The Effectiveness of Human Parathyroid Hormone and Low-Intensity Pulsed Ultrasound on the Fracture Healing in Osteoporotic Bones.

Osteoporotic fracture has become a major public health problem, and until today, the treatments available are not satisfactory. While there is growing evidence to support the individual treatment of parathyroid hormone (PTH) administration and low-intensity pulsed ultrasound (LIPUS) exposure as respectively systemic and local therapies during osteoporotic fracture healing, their effects have not yet been investigated when introduced concurrently. This study aimed to evaluate the effects of combined treatment with PTH (1-34) and LIPUS on fracture healing in ovariectomized (OVX) rats. Thirty-two, 12-week-old female Sprague-Dawley rats were OVX to induce osteoporosis. After 12 weeks, the rats underwent surgery to create bilateral mid-diaphyseal fractures of proximal tibiae. All animals were randomly divided into 4 groups (n = 8 for each): control group as placebo, PTH group, LIPUS group, and combined group. PTH group had PTH administration at a dose of 30 μg/kg/day for 3 days/week for 6 weeks. LIPUS group received ultrasound 5 days/week for 20 min/day for 6 weeks and combined group had both PTH administration and LIPUS exposure for 6 weeks. Fracture healing was observed weekly by anteroposterior radiography and micro-CT. Five weeks after the fracture, the tibia were harvested to permit histological assessments and at week 6, for mechanical property of the fracture callus. Micro-CT showed that the PTH and combined groups exhibited significantly higher BMD and trabecular bone integrity than control group at weeks 4-6. Radiography, fracture healing score and mean callus area indicated that the combined group revealed better healing processes than the individual groups. Mechanically, bending moment to failure was significantly higher in LIPUS, PTH and combined groups than in control group. These data suggest that the combined treatment of PTH and LIPUS have been shown to accelerate fracture bone healing and enhance bone properties rather than single agent therapy, and may be considered as a treatment remedy for fracture healing in postmenopausal osteoporosis.


Smad3 deficiency leads to mandibular condyle degradation via the sphingosine 1-phosphate (S1P)/S1P3 signaling axis.


Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sialadenitis.

These results suggest that LIPUS upregulates expression of AQP5 and inhibits TNF- production. Thus, LIPUS may restore secretion by inflamed salivary glands. It may synergistically activate negative feedback of NF-B signaling in response to inflammatory stimulation. Collectively, LIPUS might be a new strategic therapy for xerostomia in autoimmune sialadenitis with SS.

TNF-α stimulation of NS-SV-AC and NS-SV-DC cells resulted in a significant decrease in cell number and net fluid secretion rate (p < 0.01), whereas LIPUS treatment abolished them (p < 0.05). The expression changes of AQP5 and TNF-α were also inhibited in LIPUS treatment by blocking the NF-κB pathway. Furthermore, we found that mRNA expression of A20, a negative feedback regulator, was significantly increased by LIPUS treatment after TNF-α or interleukin 1β stimulation (NS-SV-AC, p < 0.01; NS-SV-DC, p < 0.05). In vivo LIPUS exposure to MRL/lpr mice exhibited a significant increase in both salivary flow and AQP5 expression by reducing inflammation in salivary glands (p < 0.01).


Histomorphometric analysis of overloading on palatal tooth movement into the maxillary sinus

Root penetration into the sinus and bone height reduction do not occur because new bone formation on the maxillary sinus is induced before bone resorption on the periodontal side, even though an excessive orthodontic force is applied. However, an excessive force can induce root resorption.

In the 10-g load group, the amount of tooth movement increased dramatically between days 5 and 7 and increased gradually thereafter. Tooth movement at days 5 and 7 was significantly lower in the 30-g-load group than in the 10-g load group; however, the total tooth movement at 14 days was similar in the 2 groups. An orthodontic load of 30 g stimulated bone formation on the sinus wall, but bone resorption on the periodontal ligament side was delayed because of hyalinization, which means that strong force application did not accelerate tooth movement. Moreover, some root resorption was induced by the excessive force.

American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO)


顎関節内障を有する骨格性下顎前突症に対する矯正歯科治療の一治験例

顎関節内障を有する骨格性下顎前突症に対する矯正歯科治療の一治験例

The Journal of Chu-Shikoku Orthodontic Society

中·四国矯正歯科学会雑誌


抜歯による矯正歯科治療の後戻りに対して歯科矯正用アンカースクリューを用いて再治療を行った症例

中·四国矯正歯科学会雑誌


上顎小臼歯の先天性欠損部に下顎小臼歯の移植を行った切端咬合の一治療例

上顎小臼歯の先天性欠損部に下顎小臼歯の移植を行った切端咬合の一治療例

中·四国矯正歯科学会雑誌


Effects of Decreased Occlusal Loading during Growth on the Mandibular Bone Characteristics.

Decreased loading by a soft diet causes significant changes in the mandible. However, these changes are very region-specific, probably depending on the alterations in the local loading regime. The results suggest that muscle activity during growth is very important for bone quality and morphology.


BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells.

We recently reported that brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) binds Prohibitin 2 (PHB2) in cytoplasm, thereby causing a loss of function of the PHB2 tumor suppressor in the nuclei of breast cancer cells. However, little is known regarding the mechanism by which BIG3 inhibits the nuclear translocation of PHB2 into breast cancer cells. Here, we report that BIG3 blocks the estrogen (E2)-dependent nuclear import of PHB2 via the karyopherin alpha (KPNA) family in breast cancer cells. We found that overexpressed PHB2 interacted with KPNA1, KPNA5, and KPNA6, thereby leading to the E2-dependent translocation of PHB2 into the nuclei of breast cancer cells. More importantly, knockdown of each endogenous KPNA by siRNA caused a significant inhibition of E2-dependent translocation of PHB2 in BIG3-depleted breast cancer cells, thereby enhancing activation of estrogen receptor alpha (ER). These data indicated that BIG3 may block the KPNAs (KPNA1, KPNA5, and KPNA6) binding region(s) of PHB2, thereby leading to inhibition of KPNAs-mediated PHB2 nuclear translocation in the presence of E2 in breast cancer cells. Understanding this regulation of PHB2 nuclear import may provide therapeutic strategies for controlling E2/ER signals in breast cancer cells.


Nonviral Reprogramming of Human Wharton's Jelly Cells Reveals Differences Between ATOH1 Homologues.

The transcription factor atonal homolog 1 (ATOH1) has multiple homologues that are functionally conserved across species and is responsible for the generation of sensory hair cells. To evaluate potential functional differences between homologues, human and mouse ATOH1 (HATH1 and MATH-1, respectively) were nonvirally delivered to human Wharton's jelly cells (hWJCs) for the first time. Delivery of HATH1 to hWJCs demonstrated superior expression of inner ear hair cell markers and characteristics than delivery of MATH-1. Inhibition of HES1 and HES5 signaling further increased the atonal effect. Transfection of hWJCs with HATH1 DNA, HES1 siRNA, and HES5 siRNA displayed positive identification of key hair cell and support cell markers found in the cochlea, as well as a variety of cell shapes, sizes, and features not native to hair cells, suggesting the need for further examination of other cell types induced by HATH1 expression. In the first side-by-side evaluation of HATH1 and MATH-1 in human cells, substantial differences were observed, suggesting that the two atonal homologues may not be interchangeable in human cells, and artificial expression of HATH1 in hWJCs requires further study. In the future, this line of research may lead to engineered systems that would allow for evaluation of drug ototoxicity or potentially even direct therapeutic use.


Flavones Inhibit LPS-Induced Atrogin-1/MAFbx Expression in Mouse C2C12 Skeletal Myotubes.

Muscle atrophy is a complex process that occurs as a consequence of various stress events. Muscle atrophy-associated genes (atrogenes) such as atrogin-1/MAFbx and MuRF-1 are induced early in the atrophy process, and the increase in their expression precedes the loss of muscle weight. Although antioxidative nutrients suppress atrogene expression in skeletal muscle cells, the inhibitory effects of flavonoids on inflammation-induced atrogin-1/MAFbx expression have not been clarified. Here, we investigated the inhibitory effects of flavonoids on lipopolysaccharide (LPS)-induced atrogin-1/MAFbx expression. We examined whether nine flavonoids belonging to six flavonoid categories inhibited atrogin-1/MAFbx expression in mouse C2C12 myotubes. Two major flavones, apigenin and luteolin, displayed potent inhibitory effects on atrogin-1/MAFbx expression. The pretreatment with apigenin and luteolin significantly prevented the decrease in C2C12 myotube diameter caused by LPS stimulation. Importantly, the pretreatment of LPS-stimulated myoblasts with these flavones significantly inhibited LPS-induced JNK phosphorylation in C2C12 myotubes, resulting in the significant suppression of atrogin-1/MAFbx promoter activity. These results suggest that apigenin and luteolin, prevent LPS-mediated atrogin-1/MAFbx expression through the inhibition of the JNK signaling pathway in C2C12 myotubes. Thus, these flavones, apigenin and luteolin, may be promising agents to prevent LPS-induced muscle atrophy.

Journal of Nutritional Science and Vitaminology


Low-intensity pulsed ultrasound enhances bone formation around miniscrew implants.

LIPUS enhanced bone formation around Ti and SS MSIs, enhancing the initial stability of MSIs.


Low-Intensity Pulsed Ultrasound in Dentofacial Tissue Engineering.

Oral and maxillofacial diseases affect millions of people worldwide and hence tissue engineering can be considered an interesting and clinically relevant approach to regenerate orofacial tissues after being affected by different diseases. Among several innovations for tissue regeneration, low-intensity pulsed ultrasound (LIPUS) has been used extensively in medicine as a therapeutic, operative, and diagnostic tool. LIPUS is accepted to promote bone fracture repair and regeneration. Furthermore, the effect of LIPUS on soft tissues regeneration has been paid much attention, and many studies have performed to evaluate the potential use of LIPUS to tissue engineering soft tissues. The present article provides an overview about the status of LIPUS stimulation as a tool to be used to enhance regeneration/tissue engineering. This review consists of five parts. Part 1 is a brief introduction of the acoustic description of LIPUS and mechanical action. In Part 2, biological problems in dentofacial tissue engineering are proposed. Part 3 explores biologic mechanisms of LIPUS to cells and tissues in living body. In Part 4, the effectiveness of LIPUS on cell metabolism and tissue regeneration in dentistry are summarized. Finally, Part 5 relates the possibility of clinical application of LIPUS in orthodontics. The present review brings out better understanding of the bioeffect of LIPUS therapy on orofacial tissues which is essential to the successful integration of management remedies for tissue regeneration/engineering. To develop an evidence-based approach to clinical management and treatment of orofacial degenerative diseases using LIPUS, we would like to be in full pursuit of LIPUS biotherapy. Still, there are many challenges for this relatively new strategy, but the up to date achievements using it promises to go far beyond the present possibilities.


Prevention of skeletal muscle atrophy in vitro using anti-ubiquitination oligopeptide carried by atelocollagen.

Skeletal muscle atrophy occurs when the rate of protein degradation exceeds that of protein synthesis in various catabolic conditions, such as fasting, disuse, aging, and chronic diseases. Insulin-like growth factor-1 (IGF-1) signaling stimulates muscle growth and suppresses muscle protein breakdown. In atrophied muscles, ubiquitin ligase, Cbl-b, increases and stimulates the ubiquitination and degradation of IRS-1, an intermediate in IGF-1 signaling pathway, resulting in IGF-1 resistance. In this study, we evaluated the efficacy of atelocollagen (ATCOL)-transported anti-ubiquitination oligopeptide (Cblin: Cbl-b inhibitor) (consisting of tyrosine phosphorylation domain of IRS-1) in starved C2C12 myotubes. The amount of IRS-1 protein was lower in starved versus unstarved myotubes. The Cblin-ATCOL complex inhibited IRS-1 degradation in a concentration-dependent manner. Myotubes incubated with Cblin-ATCOL complex showed significant resistance to starvation-induced atrophy (p<0.01). Furthermore, the Cblin-ATCOL complex significantly inhibited any decrease in Akt phosphorylation (p<0.01) and localization of FOXO3a to the nucleus in starved myotubes. These results suggest that Cblin prevented starvation-induced C2C12 myotube atrophy by maintaining the IGF-1/Akt/FOXO signaling. Therefore, attachment of anti-ubiquitination oligopeptide, Cblin, to ATCOL enhances its delivery to myotubes and could be a potentially effective strategy in the treatment of atrophic myopathies.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research


Aromatase controls Sjögren syndrome-like lesions through monocyte chemotactic protein-1 in target organ and adipose tissue-associated macrophages.

Several autoimmune diseases are known to develop in postmenopausal women. However, the mechanism by which estrogen deficiency influences autoimmunity is unknown. Aromatase is an enzyme that converts androgens to estrogens. Herein, we used female aromatase gene knockout (ArKO) mice as a model of estrogen deficiency to investigate the molecular mechanism that underlies the onset and development of autoimmunity. Histological analyses showed that inflammatory lesions in the lacrimal and salivary glands of ArKO mice increased with age. Adoptive transfer of spleen cells or bone marrow cells from ArKO mice into recombination activating gene 2 knockout mice failed to induce the autoimmune lesions. Expression of mRNA encoding proinflammatory cytokines and monocyte chemotactic protein-1 increased in white adipose tissue of ArKO mice and was significantly higher than that in wild-type mice. Moreover, an increased number of inflammatory M1 macrophages was observed in white adipose tissue of ArKO mice. A significantly increased monocyte chemotactic protein-1 mRNA expression of the salivary gland tissue in ArKO was found together with adiposity. Furthermore, the autoimmune lesions in a murine model of Sjögren syndrome were exacerbated by administration of an aromatase inhibitor. These results suggest that aromatase may play a key role in the pathogenesis of Sjögren syndrome-like lesions by controlling the target organ and adipose tissue-associated macrophage.


Effects of enzymatic degradation after loading in temporomandibular joint.

Synovial fluid of the joint decreases friction between the cartilage surfaces and reduces cartilage wear during articulation. Characteristic changes of synovial fluid have been shown in patients with osteoarthritis (OA) in the temporomandibular joint (TMJ). OA is generally considered to be induced by excessive mechanical stress. However, whether the changes in synovial fluid precede the mechanical overloading or vice versa remains unclear. In the present study, our purpose was to examine if the breakdown of joint lubrication affects the frictional properties of mandibular condylar cartilage and leads to subsequent degenerative changes in TMJ. We measured the frictional coefficient in porcine TMJ by a pendulum device after digestion with hyaluronidase (HAase) or trypsin. Gene expressions of interleukin-1 (IL-1), cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), type II collagen, and histology were examined after prolonged cyclic loading by an active pendulum system. The results showed that the frictional coefficient increased significantly after HAase (35%) or trypsin (74%) treatment. Gene expression of IL-1, COX-2, and MMPs-1, -3, and -9 increased significantly in enzyme-treated TMJs after cyclic loading. The increase in the trypsin-treated group was greater than that in the HAase-treated group. Type II collagen expression was reduced in both enzyme-treated groups. Histology revealed surface fibrillation and increased MMP-1 in the trypsin-treated group, as well as increased IL-1 in both enzyme-treated groups after cyclic loading. The findings demonstrated that the compromised lubrication in TMJ is associated with altered frictional properties and surface wear of condylar cartilage, accompanied by release of pro-inflammatory and matrix degradation mediators under mechanical loading.


Functional role of TGF-beta receptors during palatal fusion invitro

AbstractOBJECTIVE: Reported expression patterns for TGF- receptors (TR-I, -II, and -III) during palatogenesis suggest that they play essential roles in the mechanisms leading to palatal fusion. The purpose of this study was to compare the functions of the three TRs during palatal fusion.METHODS: Using organ culture of mouse palatal shelves, expression levels of TR-I, -II, and -III were suppressed by transfecting the siRNAs siTR-I, -II, and -III, respectively. Phosphorylation of SMAD2 was examined as an indicator of downstream signalling via each TR. Linkage between TGF- signalling and critical events in palatal fusion led to the use of, MMP-13 expression as an outcome measure for the function of the TGF- receptors.RESULTS: The siRNA treatment decreased the expression level of each receptor by more than 85%. When treated with either siTR-I or -II, palatal shelves at E13+72h were not fused, with complete clefting in the anterior and posterior regions. The middle palatal region following treatment with either siTR-I or -II had fusion from one-half or one-third of the palatal region. Treatment with siTR-III resulted in a persistent midline seam of medial edge epithelium (MEE) in the anterior region with islands of persistent MEE in the middle and posterior regions of the midline. Treatment with all three siTRs altered the pattern of SMAD2 phosphorylation. Palatal shelf cultures treated with siTR-I or -II, but not -III, showed altered MMP-13 expression levels.CONCLUSION: The ability to identify and recover MEE and palatal mesenchymal cells during palatal fusion will aid in the evaluation of the different mechanistic events regulated by each TR during palatogenesis.


Low-Intensity Pulsed Ultrasound Activates Integrin-Mediated Mechanotransduction Pathway in Synovial Cells.

Low-intensity pulsed ultrasound (LIPUS) suppresses synovial hyperplasia and synovial cell proliferation characterized for rheumatoid arthritis, but the molecular mechanisms remain unknown. The purpose of this study was to examine the mechanotransduction pathway via the integrin/mitogen-activated protein kinase (MAPK) pathway in LIPUS exposure on the synovial membrane cells. Rabbit knee synovial membrane cell line, HIG-82, was cultured with or without FAK phosphorylation inhibitor, PF-573228. One hour after stimulation with PF-573228, the cells exposed to LIPUS for 20 min or sham exposure. A possible integrin/MAPK pathway was examined by immunofluorescence and Western blotting analysis with antibodies targeting specific phosphorylation sites on intracellular signaling proteins. LIPUS exposure increased phosphorylation of FAK, JNK, ERK, and p38, but the phosphorylation was inhibited by PF-573228. In conclusion, LIPUS exposure might be involved in cell apoptosis and survival of synovial membrane cells via integrin/FAK/MAPK pathway.


The influence of unilateral disc displacement on stress in the contralateral joint with a normally positioned disc in a human temporomandibular joint: An analytic approach using the finite element method.

This suggested that a unilateral DD could affect the stresses in the unaffected (contralateral) joint during clenching, where it may lead to weakening of the tissues that keep the disc on the top of the condyle. The results may be helpful in counseling worried patients, since they give insight into possible future developments of the disorder.

In the unaffected joint of the unilateral DD model, the largest von Mises stress at the start of clenching was predicted in the inferior surface of the disc and increased by 30% during clenching. In the connective tissue the largest stress (1.16 MPa) did not reduce during clenching, in contrast to the (unaffected) joints of the reference model. In the affected joint, the largest stress was predicted in the temporal cartilage throughout clenching. In the surrounding connective tissue, the largest stress (1.42 MPa) hardly changed during clenching indicating no, or negligible, stress relaxation.

Journal of Cranio-Maxillo-Facial Surgery


Data-based prediction of soft tissue changes after orthognathic surgery: clinical assessment of new simulation software.

The aim of the present study was to evaluate the accuracy of a novel simulation software package (OrthoForecast) for predicting the soft tissue profile after orthognathic surgery. The study included 15 patients with facial asymmetry (asymmetry group), 15 with a skeletal class II jaw relationship (class II group), and 15 with a skeletal class III jaw relationship (class III group). Twenty-four feature points were digitized, and the distances between points on the predicted and actual postoperative images were compared. Thirty-seven calibrated evaluators also graded the similarity of the predicted images compared to the actual postoperative photographs. Comparisons between the predicted and actual postoperative images revealed that the mean difference between feature points was 3.1 ± 1.4 mm for the frontal images and 2.9 ± 0.8 mm for the lateral images in the asymmetry group; 2.7 ± 0.9 and 2.1 ± 1.6 mm, respectively, in the class II group; and 1.8 ± 1.2 and 1.7 ± 1.0 mm, respectively, in the class III group. More than half of the evaluators assessed the predicted images as similar to the actual postoperative images in all groups. In conclusion, OrthoForecast can be regarded as useful, accurate, and reliable software to predict soft tissue changes after orthognathic surgery.

International Journal of Oral and Maxillofacial Surgery


Torque Ratio as a Predictable Factor on Primary Stability of Orthodontic Miniscrew Implants.

TR might be related with the miniscrew success rates, and it can be used as a predictable factor on primary stability of orthodontic miniscrew implants. Miniscrew implants should be replaced if MRT is significantly lower than MIT at placement surgery.


三次元形態計測装置を用いた顔面非対称の定量的評価

三次元形態計測装置を用いた顔面非対称の定量的評価

The Journal of Chu-Shikoku Orthodontic Society

中·四国矯正歯科学会雑誌


Effects of low-intensity pulsed ultrasound on the expression of cyclooxygenase-2 in mandibular condylar chondrocytes.

LIPUS exposure inhibited IL-1-induced COX-2 expression through the integrin 1 receptor followed by the phosphorylation of ERK 1/2. Despite the restricted duration of its effect, LIPUS is suggested to be a potential candidate as a preventive and auxiliary treatment to suppress the degradation of articular chondrocytes in temporomandibular joint osteoarthritis.

Journal of Oral & Facial Pain and Headache


Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by the TALEN and CRISPR/Cas systems.

Since the establishment of embryonic stem (ES) cell lines, the combined use of gene targeting with homologous recombination has aided in elucidating the functions of various genes. However, the ES cell technique is inefficient and time-consuming. Recently, two new gene-targeting technologies have been developed: the transcription activator-like effector nuclease (TALEN) system, and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system. In addition to aiding researchers in solving conventional problems, these technologies can be used to induce site-specific mutations in various species for which ES cells have not been established. Here, by targeting the Fgf10 gene through RNA microinjection in one-cell mouse embryos with the TALEN and CRISPR/Cas systems, we produced the known limb-defect phenotypes of Fgf10-deficient embryos at the F0 generation. Compared to the TALEN system, the CRISPR/Cas system induced the limb-defect phenotypes with a strikingly higher efficiency. Our results demonstrate that although both gene-targeting technologies are useful, the CRISPR/Cas system more effectively elicits single-step biallelic mutations in mice.


歯科矯正用アンカースクリュー埋入時の安定性に関する生体力学的研究

歯科矯正用アンカースクリュー埋入時の安定性に関する生体力学的研究

Objective: The purpose of this study was to evaluate the influence of placement angle and force direction on the primary stability of orthodontic miniscrews by analyzing a novel threedimensional finite element model (FEM) approximating the interface between the screw and surrounding bone. Materials and Methods: Three-dimensional finite element models were made with 6-mm-long miniscrews in diameters of 1.2 mm. Four insertion angles ranging from 0̊ (perpendicular to the bone surface) to 45̊ were examined. A load with 2 N was applied to the center of the screw head in four directions (upward, downward and on the right and left sides). Results: For miniscrews at the same insertion angle, the stress was the highest (or lowest) under the downward (or upward) force condition. The stress increased as the insertion angle increased, except under the upward force condition. An analysis of the stress distribution in the surrounding bone showed that the most of the stress was absorbed in the cortical bone. Conclusions: The stress distribution around the miniscrew and surrounding bone during the application of orthodontic force is closely related to the force direction, and insertion angle.


Pim-2 kinase is an important target of treatment for tumor progression and bone loss in myeloma.

Pim-2 kinase is overexpressed in multiple myeloma (MM) cells to enhance their growth and survival, and regarded as a novel therapeutic target in MM. However, the impact of Pim-2 inhibition on bone disease in MM remains unknown. We demonstrated here that Pim-2 expression was also upregulated in bone marrow stromal cells and MC3T3-E1 preosteoblastic cells in the presence of cytokines known as the inhibitors of osteoblastogenesis in MM, including interleukin-3 (IL-3), IL-7, tumor necrosis factor-, transforming growth factor- (TGF-) and activin A, as well as MM cell conditioned media. The enforced expression of Pim-2 abrogated in vitro osteoblastogenesis by BMP-2, which suggested Pim-2 as a negative regulator for osteoblastogenesis. Treatment with Pim-2 short-interference RNA as well as the Pim inhibitor SMI-16a successfully restored osteoblastogenesis suppressed by all the above inhibitory factors and MM cells. The SMI-16a treatment potentiated BMP-2-mediated anabolic signaling while suppressing TGF- signaling. Furthermore, treatment with the newly synthesized thiazolidine-2,4-dione congener, 12a-OH, as well as its prototypic SMI-16a effectively prevented bone destruction while suppressing MM tumor growth in MM animal models. Thus, Pim-2 may have a pivotal role in tumor progression and bone loss in MM, and Pim-2 inhibition may become an important therapeutic strategy to target the MM cell-bone marrow interaction.Leukemia advance online publication, 30 May 2014; doi:10.1038/leu.2014.147.


Evaluation of torque moment in a novel elastic bendable orthodontic wire.

The objective of the study was to measure the torque moment delivered by a novel elastic bendable wire, Ti-Nb wire, and to compare it with nickel-titanium (Ni-Ti) and titanium-molybdenum (Ti-Mo) alloy wires. Two sizes of Ti-Nb, Ni-Ti and Ti-Mo alloy wires and 0.022-inch slot stainless steel brackets were ligated with elastic modules or ligature wires. The torque moment delivered by the various wire-bracket combinations was measured using a torque gauge at the temperature and humidity of 37°C and 50%, respectively. As the degree of applied torque and the inserted wire size increased, the torque moment gradually increased. The torque moment of Ti-Nb wires was smaller than those of Ni-Ti wires and Ti-Mo wires, at more than 20 degrees applied torque. The torque moment with wire ligation was significantly larger than those with elastic ligation.


Effects of the masticatory demand on the rat mandibular development.

The influence of masticatory loading stimulus on mandibular development is not fully clear. In this paper, experimental alterations in the daily muscle use, caused by a changed diet consistency, were continuously monitored, while adaptations in bone and cartilage were examined. It is hypothesised that decreased muscular loading will result in a decrease in the growth factor expression and mandible growth. Fourteen 21-day-old Wistar strain male rats were randomly divided into two groups and fed on either a hard or soft diet for 14 weeks. An implanted radio-telemetric device recorded continuously muscle activity of the superficial masseter muscle. Chondroblast proliferation in the condylar cartilage was identified by insulin-like growth factor-1 receptor (IGF-1r) immunostaining. Furthermore, an X-ray was taken for cephalometric analysis. In the soft-diet group, the duty time of the superficial masseter muscle at higher activity levels was significantly lower than that in the hard-diet group. This decrease in muscular loading of the jaw system was accompanied by: a significant reduction in (i) articular cartilage thickness, (ii) expression of IGF-1r immunopositive cells and (iii) mandible ramus height. In conclusion, a decrease in masticatory demand during the growth period leads to insufficient mandibular development.


Interdisciplinary treatment of a nonsyndromic oligodontia patient with implant-anchored orthodontics.

We successfully treated a nonsyndromic oligodontia patient with implant-anchored orthodontics and prosthetic restorations. A woman, age 18 years 11 months, had a straight profile and a skeletal Class I jaw-base relationship but had spaced arches because of 7 congenitally missing teeth. After leveling and alignment of the dentition, a titanium miniscrew was temporarily placed at the distal alveolus of the mandibular right first premolar, and the posterior teeth were mesialized to reduce the restorative spaces. After determination of the incisor positions, 3 dental implants were respectively inserted at the sites of the maxillary canines and the mandibular left lateral incisor with guided bone regeneration procedures. Then, screw-retained temporary prostheses were delivered after subepithelial connective tissue grafting and used for molar mesialization as absolute anchorage. After 36 months of active orthodontic treatment, an acceptable occlusion was achieved, both functionally and esthetically, with the 3 dental implants. The maxillary and mandibular molars were mesialized, but the changes of incisor position were minimal. As a result, a proper facial profile was maintained, and an attractive smile was achieved. The resultant occlusion was stable throughout a 3-year retention period. In conclusion, interdisciplinary treatment combined with orthodontics, implant surgery, and prosthodontics was useful for a nonsyndromic oligodontia patient. Especially, the new strategy-implant-anchored orthodontics-can facilitate the treatment more simply with greater predictability.

American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO)


Hypoxia-inducible factor-1 is required for transforming growth factor-1-induced type I collagen, periostin and -smooth muscle actin expression in human periodontal ligament cells.

HIF-1 is required for TGF-1-induced type I collagen, periostin and -SMA expression in human PDL cells.


Stress relaxation behaviors of articular cartilages in porcine temporomandibular joint.

In this study, we tested the compressive stress relaxation behaviors of the mandibular condylar and temporal cartilages in the porcine temporomandibular joint (TMJ). The aim was to determine the quantitative and qualitative similarities and differences of compressive stress relaxation behaviors between the two cartilages. Ten porcine TMJs were used; the articular surface was divided into 5 regions: anterior, central, posterior, lateral and medial. Compressive relaxation test was carried out at a strain level of 5% in each region of the two cartilages. The stress relaxation was monitored over a period of 5min. In all the regions of the two cartilages, the time-dependent stress relaxation curves showed a marked drop in stress within the initial 10s, which can be fitted by a standard linear viscoelastic model. The instantaneous moduli in the temporal cartilage were dominantly larger than those in the condylar cartilage, while the condylar cartilage had slightly larger relaxation moduli than the temporal cartilage except for the medial region. The both cartilages showed the regional differences in the compressive stress relaxation behavior, and in the temporal cartilage the lateral and medial regions revealed the largest values for the instantaneous and relaxation moduli. The present results demonstrate that the viscoelastic properties of compressive stress relaxation in both cartilages are region-specific, which might have an important implication for stress distribution and transmission along with the TMJ disc.


Effect of non-uniform thickness of samples in stress relaxation tests under unconfined compression of samples of articular discs.

A precise information of the biomechanical properties of soft tissues is required to develop a suitable simulation model, with which the distribution of stress and strain in the complex structures can be estimated. Many soft tissues have been mechanically characterized by stress relaxation tests under unconfined or confined compression. In general, full-thickness samples are extracted to reduce the damage in the tissue as much as possible. However, it is not guaranteed that these samples have a uniform thickness or, in other words, planar parallel faces. In particular, in the articular disc of the temporomandibular joint, many studies can be found testing full-thickness samples for which that thickness is known to be non-uniform, while making the assumption of uniaxial stress state to extract the mechanical properties from those tests. That inaccuracy may have a strong influence in some cases and needs a profound revision. The main goal of this work is to quantify the error committed in that assumption and the influence of the variation of thickness on that error in a particular test: stress relaxation tests under unconfined compression. Based on this error and defining an allowable tolerance, a criterion is established to reject samples depending on their aspect ratio.


顎顔面領域における骨治癒に対する低出力超音波パルス照射の使用経験

顎顔面領域における骨治癒に対する低出力超音波パルス照射の使用経験


Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis.

bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients.


RhoE regulates actin cytoskeleton organization in human periodontal ligament cells under mechanical stress.

These results indicate that the loss and disassembly of stress fibres due to mechanical stress are mediating RhoE signalling, without the exertion of RGS2.


Fabrications of zinc-releasing biocement combining zinc calcium phosphate to calcium phosphate cement.

Recently, zinc-releasing bioceramics have been the focus of much attention owing to their bone-forming ability. Thus, some types of zinc-containing calcium phosphate (e.g., zinc-doped tricalcium phosphate and zinc-substituted hydroxyapatite) are examined and their osteoblastic cell responses determined. In this investigation, we studied the effects of zinc calcium phosphate (ZCP) derived from zinc phosphate incorporated into calcium phosphate cement (CPC) in terms of its setting reaction and MC3T3-E1 osteoblast-like cell responses. Compositional analysis by powder X-ray diffraction analysis revealed that HAP crystals were precipitated in the CPC containing 10 or 30wt% ZCP after successfully hardening. However, the crystal growth observed by scanning electron microscopy was delayed in the presence of additional ZCP. These findings indicate that the additional zinc inhibits crystal growth and the conversion of CPC to the HAP crystals. The proliferation of the cells and alkaline phosphatase (ALP) activity were enhanced when 10wt% ZCP was added to CPC. Taken together, ZCP added CPC at an appropriate fraction has a potent promotional effect on bone substitute biomaterials.

Journal of the Mechanical Behavior of Biomedical Materials


Novel PAX9 Mutations Cause Non-syndromic Tooth Agenesis.

PAX9 is a transcription factor expressed in the tooth mesenchyme during tooth morphogenesis. In Pax9-null mice, tooth development is arrested at the bud stage. In humans, heterozygous mutations in PAX9 have been associated with non-syndromic tooth agenesis, predominantly in the molars. Here, we report 2 novel mutations in the paired domain of PAX9, a three-nucleotide deletion (73-75 delATC) and a missense mutation (C146T), in two unrelated Japanese patients with non-syndromic tooth agenesis. The individual with the 73-75del ATC mutation was missing all maxillary molars and mandibular second and third molars. The individual with the C146T mutation was missing the mandibular central incisors, maxillary second premolars, and first molars, along with all second and third molars. Both mutations affected amino acids that are highly conserved among different species and are critical for DNA binding. When both mutants were transfected to COS7 cells, nuclear localization of PAX9 proteins was not affected. However, reduced expression of the mutant proteins and almost no transcriptional activity of the target BMP4 gene were observed, suggesting haploinsufficiency of PAX9 as the cause of non-syndromic tooth agenesis.


Analysis of compressive properties of porcine temporomandibular joint disc.


Orally administered liposomal lactoferrin inhibits inflammation-related bone breakdown without interrupting orthodontic tooth movement.

Background: Bovine lactoferrin (bLF) modulates the production of tumor necrosis factor-alpha (TNF-) and inhibits alveolar bone breakdown associated with periodontitis. This study is designed to examine the effects of orally administered liposomal bLF (LbLF) on orthodontic force (OF)-induced alveolar bone remodeling during experimental tooth movement. Methods: Two groups of male Wistar rats were treated with either LbLF or control solution in drinking water 7 days before OF application. Lipopolysaccharide (LPS) was injected into the gingival sulcus in half the rats in each group. Thus, four groups: OF, OF+LbLF, OF+LPS, and OF+LPS+LbLF were established. Results: Orally administered LbLF significantly reduced apical migration of junctional epithelium in the OF and OF+LPS groups. In OF+LPS, osteoclast number in the alveolar crestal area was increased by LPS treatment, whereas osteoclast number was significantly reduced in OF+LPS+LbLF through suppression of TNF- production. Osteoclastic induction in the middle part, mainly from OF application, was not affected by LbLF administration. Inhibition of tooth movement was not induced by LbLF. Conclusions: Orally administered LbLF significantly inhibits LPS-induced alveolar bone resorption but not OF-induced bone remodeling. LbLF could be a potent therapeutic and preventive agent to control periodontal inflammation in patients undergoing orthodontic treatment.


Inhibition of Transforming Growth Factor 1 (TGF-1)/ Smad3 Signaling Decreases Hypoxia-Inducible Factor 1 (HIF-1) Protein Stability by Inducing Prolyl Hydroxylase 2 (PHD2) Expression in Human Periodontal Ligament Cells.

Background: Hypoxia-inducible factor 1 (HIF-1), the alpha subunit of the heterodimeric transcription factor HIF-1, maintains oxygen homeostasis by regulating gene expression. Under normoxic conditions, HIF-1 expression is maintained at low steady-state levels by the critical oxygen sensor prolyl hydroxylase 2 (PHD2). Transforming growth factor 1 (TGF-1) activates Smad3 signaling and contributes to HIF-1 stabilization under normoxic conditions. In chronic periodontitis, HIF-1 is expressed highly in gingival fibroblasts and upregulates inflammatory factor transcription, which promotes periodontal inflammation. Here, we investigated the effect of TGF-1/Smad3 signaling and its blockade by the specific inhibitor of Smad3 (SIS3) on HIF-1 expression and stability in human periodontal ligament (PDL) cells. Methods: We investigated the effect of TGF-1 on HIF-1 protein stability using cycloheximide (CHX). Furthermore, we analyzed HIF-1 expression, PHD2 expression and Smad3 phosphorylation following TGF-1 stimulation in the presence or absence of SIS3. Results: The half-life of HIF-1 was prolonged in TGF-1-treated cells. TGF-1 treatment induced HIF-1 gene expression and enhanced HIF-1 protein stability while decreasing PHD2 expression and activating Smad3 phosphorylation. Notably, HIF-1 protein expression was not detectable prior to TGF-1 stimulation. Furthermore, SIS3 treatment abrogated Smad3 phosphorylation, impaired TGF-1-induced HIF-1 gene expression and protein stability and stimulated TGF-1-mediated PHD2 inhibition. Conclusions: These results demonstrate that HIF-1 transcription and protein synthesis are controlled by TGF-1/Smad3 signaling, whereas HIF-1 protein stability is controlled by PHD2, which is regulated by TGF-1/Smad3 signaling.


Orthodontic occlusal reconstruction after conservative treatment of unicystic ameloblastoma in an adolescent patient: 10-year follow-up.

Conservative treatment of an ameloblastoma often requires an occlusal reconstruction. In this article, we report the successful interdisciplinary treatment of a 14-year-old girl with a unicystic ameloblastoma in the mandible. One year after the marsupialization, enucleation with bone curettage was performed with extraction of the impacted third molar, but the proximal second molar could be maintained. The conservative treatment required long-term use of an obturator, and it caused a total open bite. Additionally, the patient genetically had a Class II malocclusion with severe crowding. Consequently, orthodontic treatment was performed after 4 premolar extractions. There was no recurrence of the ameloblastoma 10 years after the enucleation.

American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO)


Role of Masseter Muscle 2-Adrenergic Signaling in Regulation of Muscle Activity, Myosin Heavy Chain Transition, and Hypertrophy.

Chronic administration of clenbuterol (CB), a lipophilic 2-adrenoceptor (2-AR) agonist, induces skeletal muscle hypertrophy and slow-to-fast fiber-type transitions in mammalian species, but the mechanism and pathophysiological roles of these changes have not been explored. Here, we examined the effects of CB not only on masseter muscle mass, fiber diameter, and myosin heavy chain (MHC) composition, but also on daily muscle activity, a factor influencing muscle phenotype, by means of electromyogram analysis in rats. MHC transition towards faster isoforms was induced by 2-week CB treatment. In addition, daily duty time was increased at 1 day, 1 week, and 2 weeks after the start of CB treatment and its increase was greater at high activity level (6-fold) than at low activity level (2-fold). In order to examine whether these effects of CB were mediated through muscle or CNS 2-AR stimulation, we compared these effects of CB with those of salbutamol (SB), a hydrophilic 2-AR agonist. SB treatment induced masseter hypertrophy and MHC transition, like CB, but did not increase daily activity. These results suggest that CB-mediated slow-to-fast MHC transition with hypertrophy was induced through direct muscle 2-AR stimulation, but the increase of daily duty time was mediated through the CNS.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.12271FP].


Hypodontiaを伴う二卵性双生児の下顎後退症例

Hypodontiaを伴う二卵性双生児の下顎後退症例

The Journal of Chu-Shikoku Orthodontic Society

中·四国矯正歯科学会雑誌


三次元デジタルモデルを用いた片側性口唇口蓋裂患者の咬合評価に関する検討 第二報 デジタルツールが三次元デジタル模型の評価に及ぼす影響

中·四国矯正歯科学会雑誌


上下顎同時移動術により下顔面高の過大を改善した骨格性下顎前突症例

上下顎同時移動術により下顔面高の過大を改善した骨格性下顎前突症例


Local applications of myostatin-siRNA with atelocollagen increase skeletal muscle mass and recovery of muscle function.

These data suggest local administration of Mst-siRNA/ATCOL complex could lead to skeletal muscle hypertrophy and recovery of motor disability in mCAV-3Tg mice. Therefore, ATCOL-mediated application of siRNA is a potential tool for therapeutic use in muscular atrophy diseases.


Down-regulation of Smad3 Accelerates Palatal Wound Repair.

Smad3-deficient mice exhibit accelerated re-epithelialization and tissue remodeling during palatal wound repair. In addition, transforming growth factor beta 1 (TGF-1) and other inflammatory factors are down-regulated compared with those in wild-type mice. The aim of this study was to examine whether targeting of Smad3 with small interfering RNA (siRNA) accelerates wound-healing and inhibits wound contraction in palatal mucoperiosteal wounds. An initial histological examination of wound closure in mouse palates treated with Smad3-targeted siRNA vs. a scrambled siRNA found that wound-healing was accelerated when levels of Smad3 were decreased. Furthermore, with real-time PCR, mRNA levels of Smad3, TGF-1, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 (MIP-1) were found to be significantly down-regulated in palatal tissue treated with Smad3-targeted siRNA vs. a control siRNA. Protein and mRNA levels of -smooth-muscle actin (-SMA), type I collagen, and fibronectin were also lower in palates treated with Smad3-targeted siRNA vs. control siRNA. Taken together, these results indicate that down-regulation of Smad3 expression by siRNA can accelerate wound-healing and may inhibit wound contraction. Therefore, siRNA-targeted inhibition of Smad3 may represent a valuable therapeutic tool for palatal mucoperiosteal wound-healing.


Dynamic compressive properties of articular cartilages in the porcine temporomandibular joint.

The mandibular condylar and temporal cartilages in the temporomandibular joint (TMJ) play an important role as a stress absorber during function. However, relatively little information is available on its viscoelastic properties in dynamic compression, particularly in a physiological range of frequencies. We hypothesized that these properties are region-specific and depend on loading frequency. To characterize the viscoelastic properties of both cartilages, we performed dynamic indentation tests over a wide range of loading frequencies. Nine porcine TMJs were used; the articular surface was divided into five regions: anterior; central; posterior; medial and lateral. Sinusoidal compressive strain was applied with an amplitude of 1.0% and a frequency range between 0.01 and 10Hz. In both cartilages, the dynamic storage modulus increased with frequency, and the value was the highest in the lateral region. These values of E' in the temporal cartilage were smaller than those in the mandibular condylar cartilage in all five regions except the lateral region. The Loss tangent values were higher in the temporal cartilage (0.35-0.65) than in the mandibular condylar one (0.2-0.45), which means that the temporal cartilage presents higher viscosity. The present results suggest that the dynamic compressive moduli in both cartilages are region-specific and dependent on the loading frequency, which might have important implications for the transmission of load in the TMJ.

Journal of the Mechanical Behavior of Biomedical Materials


Longitudinal changes in the height and location of bone bridge from autogenous iliac bone graft in patients with cleft lip and palate.


Stress analysis in human temporomandibular joint affected by anterior disc displacement during prolonged clenching.

Parafunctional habits, such as prolonged clenching and bruxism, have been associated with dysfunctional overloading in the temporomandibular joint (TMJ). In this study, stress distributions in the TMJ were analysed during prolonged clenching, using three-dimensional finite element (FE) models of the TMJ with and without disc displacement. The aim of this study was to investigate stress distribution of the cartilaginous tissues in the TMJ with and without disc displacement. Finite element models were developed on the basis of magnetic resonance images from two subjects with and without anterior disc displacement. Condylar movements recorded during a 5-min clenching were used as the loading condition for stress analysis. In the asymptomatic model, the highest von Mises stresses were located in the lateral area (4·91 MPa) of the disc surfaces, and after 5-min clenching, the higher stresses were still located at the lateral area (3·65 MPa). In all the cartilaginous tissues, 30-50% of stress reduction occurred during 5-min clenching. In contrast, the von Mises stress in the cartilaginous tissues of the symptomatic model with disc displacement was markedly lower, compared with the asymptomatic model. However, in the condylar cartilage, stress relaxation during clenching was not recognised. Furthermore, relatively high stresses were observed in the retrodiscal tissues throughout clenching. The present results indicate that disc position could be involved in the stress distribution of the TMJ components during prolonged clenching.


Ultrasound modulates the inflammatory response and promotes muscle regeneration in injured muscles.

The purpose of this study was to examine the effect of ultrasound on inflammatory skeletal muscle in vitro and in vivo. C2C12 cells were cultured in medium with or without TNF-α or IL-1β. After stimulation with cytokines, the cells received ultrasound or sham exposure. Furthermore, the tibialis anterior (TA) muscle in C57BL/6 mice injured by cardiotoxin (CTX) were dissected after a series of ultrasound treatments and examined. Exposure of C2C12 cells to ultrasound resulted in down-regulation of cyclooxygenase-2 (COX-2) mRNA and protein expression induced by TNF-α or IL-1β, and up-regulated myogenin mRNA and protein depressed by TNF-α or IL-1β. In injured TA muscle induced by CTX, ultrasound caused increase of COX-2 mRNA at 1 day after ultrasound treatment, however, at day 5, reduction of COX-2 mRNA and protein. At day 5, ultrasound caused increase of myogenin mRNA and protein, increase of fast myosin protein, and increase of paired-box transcription factor 7 positive cells. At day 7, the cross-sectional area of myofibers in the ultrasound exposure side was significantly larger than that on the control side. In conclusion, ultrasound stimulation may be a better candidate as a medical remedy to promote myogenesis in inflammatory muscle states, such as muscle injury.


Ultrasound stimulation attenuates resorption of tooth root induced by experimental force application.

Root resorption is an adverse outcome of orthodontic tooth movement. However, there have been no available approaches for the protection and repair of root resorption. The aim of this study was to evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on root resorption during experimental tooth movement and the effects of LIPUS in the RANKL/OPG mechanism in osteoblasts and cementoblasts in vitro. Twenty four Wistar strain male rats of 12-week-old were used in this study. The upper first molars were subjected to experimental movement in the mesial direction for 1-3weeks. Through the experimental periods, the right upper first maxillary molar was exposed to LIPUS (LIPUS group) every day for 1, 2 or 3weeks. The nature of root resorption was observed and then quantified by histomorphometric analysis. In the 2weeks period, significantly greater amount of tooth movement was observed in the LIPUS group (p<0.05). In addition, LIPUS group showed less root resorption lacunae and lower number of odontoclasts. In the period of 3weeks, LIPUS group presented significantly shorter length of root resorption lacunae and smaller amount of root resorption area (p<0.01). The number of odontoclasts and osteoclasts was also significantly lower in the LIPUS group (p<0.01 and p<0.05, respectively). However, no significant differences could be found regarding the amount of tooth movement. It is shown that LIPUS exposure significantly reduced the degree of root resorption during tooth movement without interrupting tooth movement. In vitro experiments showed that MC3T3-1 constitutively expressed higher levels of RANKL and RANTES mRNA comparing to OCCM-30. However, OPG mRNA expression was much higher in OCCM-30. LIPUS stimulation significantly increased the mRNA expression of RANKL in MC3T3-E1 at 4 (p<0.01) and 12h (p<0.05), although OPG mRNA expression was not affected by LIPUS. In contrast, the expression of RANKL and OPG mRNAs were both significantly increased by LIPUS in OCCM-30 at 12h (p<0.01). Moreover, LIPUS application suppressed the up-regulation of RANKL mRNA induced by compression force in OCCM-30, but no similar effect could be observed in MC3T3-E1. In conclusion, it is suggested that LIPUS exposure significantly reduces root resorption by the suppression of cementoclastogenesis by altering OPG/RANKL ratio during orthodontic tooth movement without interfering tooth movement. LIPUS may be an effective tool to prevent root resorption during tooth movement and is applicable to clinical use in near future.


Induction of Rapid T Cell Death and Phagocytic Activity by Fas-Deficient lpr Macrophages.

Peripheral T cells are maintained by the apoptosis of activated T cells through the Fas-Fas ligand system. Although it is well known that normal T cells fail to survive in the Fas-deficient immune condition, the molecular mechanism for the phenomenon has yet to be elucidated. In this study, we demonstrate that rapid cell death and clearance of normal T cells were induced by Fas-deficient lpr macrophages. Transfer of normal T cells into lpr mice revealed that Fas expression on donor T cells was promptly enhanced through the IFN-/IFN-R. In addition, Fas ligand expression and phagocytic activity of lpr macrophages were promoted through increased NF-B activation. Controlling Fas expression on macrophages plays an essential role in maintaining T cell homeostasis in the peripheral immune system. Our data suggest a critical implication to the therapeutic strategies such as transplantation and immunotherapy for immune disorder or autoimmunity related to abnormal Fas expression.


Measurements of the torque moment in various archwire-bracket-ligation combinations

The torque moment generated by third-order bends is important for tooth movement. The purpose of this study was to measure the torque moment that can be delivered by various archwire and bracket combinations at the targeted tooth. Stainless steel (SS) upper brackets with 0.018 and 0.022 inch slots, two sizes of nickel-titanium (Ni-Ti) alloy wires, and three sizes of SS wires for each bracket were used. The wire was ligated with elastics or wire. The torque moment delivered by the various archwire-bracket-ligation combinations was measured using a torque gauge. Statistical analysis was undertaken using analysis of variance (multiple comparison tests and post hoc using Tukey's honestly significant difference test. The torque moment increased as the degree of torque and wire size increased. There was no significant difference in torque moment between the SS and Ni-Ti wires at lower or higher than 40 degrees torque. The torque moment with wire ligation was significantly larger than that with elastic ligation with 0.016 × 0.022 and 0.017 × 0.025 inch Ni-Ti wires in the 0.018 inch slot brackets and the 0.017 × 0.025 and 0.019 × 0.025 inch SS and Ni-Ti wires in the 0.022 inch slot brackets. However, there was no significant difference in torque moment between either ligation method when using the full slot size wires.


Current status of low intensity pulsed ultrasound for dental purposes.

Over the past few years, tissue engineering applied to the dental field has achieved relevant results. Tissue engineering can be described by actions taken to improve biological functions. Several methods have been described to enhance cellular performance and low intensity pulsed ultrasound (LIPUS) has shown to play an important role in cell metabolism. The present article provides an overview about the current status of LIPUS as a tissue engineering tool to be used to enhance tooth and periodontal regeneration.


The region-dependent dynamic properties of porcine temporomandibular joint disc under unconfined compression.

In this study, the dynamic compressive properties in five different regions of the porcine temporomandibular joint (TMJ) disc are investigated over a wide range of loading frequencies. The aim was, thus far, to evaluate the regional difference and the frequency-related effect of the applied load on these properties. Eleven porcine TMJ discs were used; each disc was divided into 5 regions, anterior, central, posterior, lateral and medial. Sinusoidal compressive strain was applied with an amplitude of 1.0% and a frequency range between 0.01 and 10Hz. The dynamic storage and loss moduli increase with frequency, the highest values being attained at the posterior region, followed by the central and anterior regions. Loss tangent, tan, ranged from 0.20 to 0.35, which means that the disc is primarily elastic in nature and has a small but not negligible viscosity. The present results suggest that the dynamic viscoelastic compressive modulus is region-specific and depends on the loading frequency, thus having important implications for the transmission of load to the TMJ.


Fas-Independent T-Cell Apoptosis by Dendritic Cells Controls Autoimmune Arthritis in MRL/lpr Mice

BACKGROUND: Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-B ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity. METHODS AND FINDING: Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4(+) T, B, and CD4(-)CD8(-) double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice. CONCLUSION: These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice.


Orthognathic and orthodontic treatments for TMJ-osteoarthritis with jaw deformity


Skeletal anchorage facilitates the treatment of jaw deformities with vertical discrepancy: its application and limitations


Segmental distraction osteogenesis with modified LeFort II osteotomy for a patient with craniosynostosis

In this article, we report successful orthodontic treatment combined with segmental distraction osteogenesis after a modified LeFort II osteotomy in a patient with craniosynostosis. An 8-year-old boy diagnosed with craniosynostosis had a dished-in face, an anterior crossbite, and a skeletal Class III jaw relationship because of midfacial hypoplasia. At the age of 13 years 6 months, the maxillary second and mandibular first premolars were extracted, and leveling and alignment of both arches was started with preadjusted edgewise appliances. At age 14 years 11 months, the patient had a modified LeFort II osteotomy, and the maxillary segment was advanced 7 mm and fixed to the zygomatic bone. At the same time, segmental distraction osteogenesis was started with a rigid external distraction system, and the nasal segment was advanced for 20 days at a rate of 1.0 mm per day. The total active treatment period was 40 months. As a result of the modified segmental distraction osteogenesis, significant improvement of his severe midfacial hypoplasia was achieved without excessive advancement of the maxillary dentition. Both the facial profile and the occlusion were stable after 1 year of retention. However, the nasal segment relapsed 1.4 mm during the 1.5 years after the segmental distraction osteogenesis. Evaluation of the stability and retention suggests that some overcorrection in midfacial advancement is recommended.

American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO)


Assessment of occlusal relationship in unilateral cleft lip and palate patients using 3-dimensional digital models

三次元デジタルモデルを用いた片側性口唇裂口蓋裂患者の咬合評価に関する検討

Journal fo Japanese Cleft Palate Association


d-Dopachrome tautomerase promotes IL-6 expression and inhibits adipogenesis in preadipocytes.

We previously identified d-dopachrome tautomerase (DDT) as a novel adipokine whose mRNA levels in adipocytes are negatively correlated with obesity-related clinical parameters, and which acts on adipocytes to regulate lipid metabolism. Here we investigated functions of DDT on preadipocytes. Recombinant DDT (rDDT) enhanced both the expression and secretion of interleukin-6 (IL-6) in SGBS cells, a human preadipocyte cell line. Treatment with rDDT increased levels of phosphorylated ERK1/2, but not p38, in SGBS cells, and rDDT-induced IL-6 mRNA expression was attenuated by pretreatment with an ERK inhibitor, U0126. Knockdown of CD74, but not CD44, inhibited rDDT-induced IL-6 mRNA expression in SGBS cells. These results suggested that the rDDT-induced IL-6 expression in preadipocytes occurred through the CD74-ERK pathway. Furthermore, in SGBS cells subjected to adipogenic induction, rDDT decreased the amount of triacylglycerol, number of cells with oil droplets, and levels of mRNA encoding adipocyte marker proteins. Increased expression of CCAAT/enhancer binding protein families and peroxisome proliferator-activated receptor 2 during adipogenesis was inhibited in the cells treated with rDDT. These results suggested DDT to inhibit adipogenesis by suppressing the expression of genes encoding adipogenic regulators in preadipocytes.


アンキローシスを伴う歯に対して外科的亜脱臼後の牽引処置を行った一症例

アンキローシスを伴う歯に対して外科的亜脱臼後の牽引処置を行った一症例

The Journal of Chu-Shikoku Orthodontic Society

中·四国矯正歯科学会雑誌


徳島大学病院矯正歯科における顎変形症患者の臨床統計学的検討

徳島大学病院矯正歯科における顎変形症患者の臨床統計学的検討

中·四国矯正歯科学会雑誌


Management of acquired open bite associated with temporomandibular joint osteoarthritis using miniscrew anchorage

This article reports the orthodontic treatment of a patient with skeletal mandibular retrusion and an anterior open bite due to temporomandibular joint osteoarthritis (TMJ-OA) using miniscrew anchorage. A 46-year-old woman had a Class II malocclusion with a retropositioned mandible. Her overjet and overbite were 7.0 mm and -1.6 mm, respectively. She had limited mouth opening, TMJ sounds, and pain. Condylar resorption was observed in both TMJs. Her TMJ pain was reduced by splint therapy, and then orthodontic treatment was initiated. Titanium miniscrews were placed at the posterior maxilla to intrude the molars. After 2 years and 7 months of orthodontic treatment, an acceptable occlusion was achieved without any recurrence of TMJ symptoms. The retropositioned mandible was considerably improved, and the lips showed less tension upon lip closure. The maxillary molars were intruded by 1.5 mm, and the mandible was subsequently rotated counterclockwise. Magnetic resonance imaging of both condyles after treatment showed avascular necrosis-like structures. During a 2-year retention period, an acceptable occlusion was maintained without recurrence of the open bite. In conclusion, correction of open bite and clockwise-rotated mandible through molar intrusion using titanium miniscrews is effective for the management of TMJ-OA with jaw deformity.


Severity of alveolar cleft before palatoplasty affects vertical maxillofacial growth in 6-year-old patients with complete unilateral cleft lip and palate.

In this study, we investigated the association between the severity of alveolar clefts in infants and the succeeding maxillofacial growth in patients affected by complete unilateral cleft lip and palate. The subjects were 35 nonsyndromic patients affected by unilateral cleft lip and palate (n = 27) or bilateral cleft lip and palate (n = 8). Plaster models and lateral cephalograms taken at 6 years of age were analyzed and compared with the Japanese norms. In the unilateral cleft lip and palate patients, the relationship between the width of the alveolar cleft before palatoplasty and the skeletal characteristics was also explored. Significant deficiencies of the posterior maxilla and steep palatal planes were noted in both the unilateral and bilateral cleft lip and palate patients. However, they were not clearly observed in the unilateral cleft lip and palate patients born with a small alveolar cleft and were correlated with the severity of alveolar cleft in infancy. Neither cleft type nor the severity of the alveolar cleft was implicated in the maxillary arch form in childhood, but the growth of the alveolar height on the cleft side was less in the unilateral cleft lip and palate patients born with a large alveolar cleft. The severity of the alveolar cleft before palatoplasty affects the succeeding vertical maxillofacial growth in patients affected by unilateral cleft lip and palate; this suggests the necessity of a different diagnosis and treatment in unilateral cleft lip and palate patients according to the severity of the alveolar cleft in infancy.


Long-term stability of conservative orthodontic treatment in a patient with rheumatoid arthritis and severe condylar resorption.

Rheumatoid arthritis is a chronic inflammatory condition that can result in progressive destruction of the articular surfaces of the joints, including the temporomandibular joint. The purpose of this article is to report the conservative correction of a Class II malocclusion in a woman with rheumatoid arthritis. The patient was 32 years 6 months old at the start of treatment. She had a convex profile and a skeletal Class II jaw-base relationship caused by severe condylar resorption. An anterior open bite of -2.0 mm and an excessive overjet of 10.0 mm were observed. Severe crowding was shown in the mandibular incisors. After 8 months of splint therapy, all first premolars were extracted, and 0.018-in preadjusted edgewise appliances were placed in both arches. Class II elastics were used during space closure. After 41 months of active orthodontic treatment, an acceptable occlusion was achieved, and the facial profile was considerably improved. From the cephalometric evaluations, the mandible was rotated counterclockwise, and the mandibular plane angle was significantly decreased. However, the anteroposterior position of the chin was not changed. The condylar resorption was not changed during and after orthodontic treatment. Conclusively, the proper facial profile was maintained, and the occlusion was stable after a 5-year retention period. Our results suggest the possibility of compromised treatment in a Class II malocclusion with an anterior open bite because of rheumatoid arthritis.


Mechanical stress induces bone formation in the maxillary sinus in a short-term mouse model.

OBJECTIVES: Clinicians occasionally face the challenge of moving a tooth through the maxillary sinus. The objective of this study was to evaluate tissue remodeling during tooth movement into the maxillary sinus, more specifically as regards to bone formation. MATERIALS AND METHODS: The maxillary first molar of 20 male mice was moved toward the palatal side by a nickel-titanium super elastic wire for 1 to 14 days, and the bone remodeling around the root was evaluated using histomorphometry and immunodetection of bone-restricted Ifitm-like (Bril) protein, a novel marker of active bone formation. RESULTS: When mechanical stress was applied to the tooth, the periodontal ligament on the palatal side was immediately compressed to approximately half of its original width by the tipping movement of the tooth. At the same time, osteoblasts deposited new bone on the wall of the maxillary sinus prior to bone resorption by osteoclasts on the periodontal side, as evidenced by the high level of expression of Bril at this site. As a result of these sequential processes, bone on the sinus side maintained a consistent thickness during the entire observation period. No root resorption was observed. CONCLUSIONS: Bone formation on the surface of the maxillary sinus was evoked by mechanotransduction of mechanical stress applied to a tooth over a 2-week period, and was induced ahead of bone resorption on the periodontal ligament side. CLINICAL RELEVANCE: Mechanical stress can be exploited to induce bone formation in the maxillary sinus so that teeth can be moved into the sinus without losing bone or causing root damage.


Early postoperative evaluation of secondary bone grafting into the alveolar cleft and its effects on subsequent orthodontic treatment

Alveolar bone grafting is a standard procedure used to achieve good occlusion for both functional and aesthetic purposes in patients with cleft lip and palate. At the past, main methods used to evaluate bone bridge formation after bone grafting are radiographs, such as dental, occlusal, and panoramic. To evaluate bone bridge both qualitatively and quantitatively, we used CT scans (conventional and QCT). Quantitative computed tomography (QCT) has previously been used for measuring bone mineral density of the lumbar vertebrae. The study comprised 26 male and 15 female patients who underwent alveolar bone grafting. We analyzed bone bridge with regard to four factors: marginal bone level, vertical height, anteroposterior bone width and bone mineral density using dental radiographs, and CT scans such as conventional and QCT. The clinical results of orthodontic treatment were evaluated more than 2 years postoperatively. Orthodontic treatment was considered to be successful when the bone bridge satisfied the following criteria: marginal bone level >= 3, vertical height >= 6.5 mm, anteroposterior bone width >= 5 mm, and bone mineral density < 350 mg Ca(5) (PO(4)) OH/mL. we could predict the prognosis of patients' orthodontic treatment in early stage after bone grafting.

The Journal of Medical Investigation : JMI


Low-Intensity Pulsed Ultrasound Reduces the Inflammatory Activity of Synovitis.

The purpose of this study was to examine the effect of low-intensity pulsed ultrasound (LIPUS) on the cell proliferation and growth of synovial membrane cells stimulated with inflammatory cytokines, and to evaluate the effectiveness of LIPUS treatment of synovitis in the knee joints of animal models for rheumatoid arthritis. The rabbit knee synovial membrane cell line, HIG-82, was cultured in medium with or without IL-1β or TNF-α. Four hours after stimulation with the cytokines, the cells received LIPUS or sham exposure. Cell proliferation and growth were then analyzed. Using MRL/lpr mice, the anti-inflammatory effects of LIPUS were also evaluated in vivo. Stimulation with proinflammatory cytokines significantly up-regulated cell proliferation which was significantly down-regulated by LIPUS exposure. In MRL/lpr mice, exposure of knee joints to LIPUS caused a significant reduction of histological damage compared to the control. Histological lesions were significantly reduced in the joints treated with LIPUS for 3 weeks. Cox-2-positive cells in the knee joints treated with LIPUS were markedly decreased compared to the control joints. Therefore, LIPUS stimulation may be a medical treatment for joint inflammatory diseases, such as synovitis.


Long-term stability of LeFort III distraction osteogenesis with a rigid external distraction device in a patient with Crouzon syndrome.

A 6-year-old boy, diagnosed with Crouzon syndrome, had moderate exorbitism, a concave profile, an anterior crossbite of -4.0 mm, and a skeletal Class III jaw-base relationship caused by midfacial hypoplasia. At age 8 years 9 months, a LeFort III osteotomy was performed, and distraction osteogenesis was immediately started with the rigid external distractor system. The midface was advanced approximately 10.0 mm for 6 days, including overcorrection. After the distraction, a reverse headgear was used for 6 years to prevent relapse and to accelerate expected growth. At age 16 years 5 months, after extraction of the maxillary first premolars and mandibular third molars, 0.022-in preadjusted edgewise brackets were placed to treat the edge-to-edge incisor relationship and minor crowding. After 13 months of treatment, the facial profile was significantly improved, and an acceptable occlusion was achieved. During the 9-year observation period after the distraction, acceptable facial growth occurred, and no relapse of the maxillary advancement was observed. However, syndrome-specific growth and methodologically induced relapse should be considered when planning a LeFort III distraction in children for the treatment of Crouzon syndrome.

American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO)


Non-linear Viscoelastic Model for Behaviour Characterization of Temporomandibular Joint Discs

Generally, the complex behaviour of the disc ofthe temporomandibular joint (TMJ) cannot be adequatelyrepresented using linear elastic or linear viscoelasticmodels. Since the disc is regularly subjected to large strainand stress levels, the study of its non-linear response undercompression is of practical interest, especially for analysisof medical dysfunctions. With this aim, relaxation andcreep tests were carried out using round specimens ofdiameters ranging between 4 and 6 mm cut off from thecentral, anterior, posterior, lateral and medial zones ofporcine discs to investigate the regional mechanicalproperties differences. The experimental data results arefitted using Prony series, based on generalized Maxwelland Kelvin models, allowing the relaxation and creepmoduli to be represented, respectively, as a function of thestrain and stress. The results show that the non-linearmaterial behaviour of this biological tissue is properlydescribed by the proposed models, to be consideredsubsequently in numerical calculations.


PERIOSTIN regulates MMP-2 expression via the αvβ3 integrin/ERK pathway in human periodontal ligament cells.

OBJECTIVE: During orthodontic tooth movement, activation of the vascular system in the compressed periodontal ligament (PDL), which becomes hypoxic, is essential for periodontal tissue remodelling. PERIOSTIN, an extracellular matrix protein, is expressed in PDL and its concentration is increased on the compressive side during orthodontic tooth movement. PERIOSTIN promotes angiogenesis through upregulation of matrix metalloproteinase (MMP)-2, which has been shown to be expressed via αvβ3 integrin/extracellular signal-related kinase (ERK) signalling pathway and vascular endothelial growth factor (VEGF). Therefore, we hypothesized that hypoxia-induced PERIOSTIN promotes MMP-2 expression via αvβ3 integrin/ERK signalling and VEGF in PDL cells. METHODS: Human PDL cells were cultured in condition medium containing desferrioxamine (DFO) to mimic hypoxia. The total RNA, cell lysates or supernatant were collected, and MMP2 and VEGF expression, PERIOSTIN expression and ERK phosphorylation, and MMP-2 activity were analysed by real-time RT-PCR, western blot analysis, and zymography, respectively. A recombinant human PERIOSTIN or PERIOSTIN siRNA was applied to the cells, then the total RNA was extracted to measure MMP-2 and VEGF expression. The cells were treated with αvβ3 integrin-blocking antibody or ERK inhibitor followed by PERIOSTIN stimulation. MMP-2 expression was measured by real-time RT-PCR. RESULTS: PERIOSTIN was upregulated in a time-dependent manner in human PDL cells treated with DFO, a chemical hypoxia mimic. MMP-2 and VEGF expression, and MMP-2 activity were increased by DFO or PERIOSTIN treatment, and decreased by PERIOSTIN silencing. PERIOSTIN treatment also induced ERK phosphorylation, and PERIOSTIN-induced MMP-2 was reduced by αvβ3 integrin-blocking antibody or ERK inhibitor. CONCLUSION: These data suggest that PERIOSTIN upregulates MMP-2 expression via the αvβ3 integrin/ERK signalling pathway and VEGF expression in human PDL cells.


A hospital-based survey of TMD patients at Tokushima University Hospital

徳島大学病院における顎関節症患者の特徴に関する調査-男女比，年齢構成と受診期間-

Objective: The purpose of this research was to clarify the characteristics of TMD patients at Tokushima University Hospital and to investigate the effects of clinical sampling bias. Materials and Methods: Recorded data of selected TMD patients (1,083 cases, average age 39.2±19.4, male : female=1 : 2.4) from the TMD report system in the digital chart system of the hospital and new patients of Tokushima University Hospital Dental Division (24,588 cases, average age 43.0±23.5, male : female=1 : 1.4) were analyzed in terms of the age distribution, the male to female ratio and the treatment period. Results: The male to female ratio of both groups was significantly different (chi-square test: p<0.001). The age distribution of TMD patients was bimodal. Peak age groups were 15-24 and 55-59 years old. In comparison with the new patients group, there were many TMD patients among the 15-34 year-old group, but few in the 60-84 year-old group. On the contrary, the age distributions were different from those of the general population in Tokushima prefecture (Population Census 2005, Ministry of Internal Affairs and Communications), particularly among the middle aged. This comparison indicated that the bimodal age distribution of TMD patients might reflect a sampling bias of the clinic-based sample. For example, the limited office hours for outpatient care of the university hospital might result in a socio-economic bias for working-age patients and cause an apparent bimodal distribution. Regarding treatment period, about 80% of patients completed regular outpatient treatment within 90 days and about 90% of patients completed it within 180 days. On the other hand, there were 52 cases (4.8% of 1,083 cases) who received outpatient treatment for more than 1 year. Conclusion: The characteristics of TMD patients at Tokushima University Hospital were investigated, including the effects of clinical sampling bias.

目的:徳島大学病院で使用している顎機能レポートシステム記録から受診患者の特徴と経過を把握し，さらに臨床サンプルにおけるバイアスの影響について検討を行うことを目的とした． 対象および方法:対象は徳島大学病院を顎関節症または関連疾患で受診し，顎機能レポートシステムに記録があり，なおかつ選択基準を満たした解析対象群1,083例(男女比1:2.4)と歯科診療部門をほぼ同期間に受診した一般初診患者群24,588例(男女比1:1.4)である．解析項目は年齢構成，男女比，受診期間などである． 結果および考察:解析対象群の年齢構成は15∼24歳と55∼59歳にピークのある二峰性を示した．一般初診患者群との比較では，解析対象群の15∼34歳が多い傾向を示す一方，60歳以上では少ない傾向を示し，男女比も有意に異なっていた(χ2検定:p<0.001)．年齢分布については，一般住民の年齢構成(総務省「平成17年国勢調査」)に対し一般初診患者群，解析対象群とも青壮年層で少ない傾向を示し，大学病院受診患者というサンプリングバイアスが見かけ上の二峰性を生じさせていた可能性が考えられた．経過としては90日以内で約80%，180日以内で約90%が診療終了となる一方，通院1年以上の長期症例が約5%存在した． 結論:大学病院における顎関節症患者の特徴および経過について明らかにするとともに，サンプリングバイアスの影響について検討を行った．

Journal of the Japanese Society for the Temporomandibular Joint


徳島大学病院矯正歯科における患者の動向調査

徳島大学病院矯正歯科における患者の動向調査

The Journal of Chu-Shikoku Orthodontic Society

中·四国矯正歯科学会雑誌


インプラント固定に関する臨床統計学的研究

インプラント固定に関する臨床統計学的研究

中·四国矯正歯科学会雑誌


過去25年間に徳島大学病院矯正歯科に来院した口唇裂・口蓋裂患者の臨床統計学的調査

中·四国矯正歯科学会雑誌


Ameloblastin is not implicated in bone remodelling and repair.

Ameloblastin (AMBN) is an enamel matrix protein produced by ameloblasts. It has been suggested that AMBN might also be implicated in craniofacial bone formation. Our objective was to determine whether AMBN has an effect on osteogenic mineralisation and influences bone remodelling and repair. MC3T3-E1 cells were screened for endogenous expression of enamel proteins using real time PCR. Various osteogenic cells were infected with lentivirus encoding for AMBN and protein expression was verified using immunochemistry. Cultures were stained with alizarin red and mineralisation was quantified. Healing bone was probed for expression of AMBN by DNA microarray analysis. Tooth extraction, experimental tooth movement (ETM), and creation of a non-critical size bone defect in the tibia (BDT) were carried out in wild type and AMBNΔ5-6 mutant mice. Tissues were processed for immunolabelling of AMBN and Bril, an osteoblast specific protein associated with active bone formation. MC3T3-E1 cells and healing bone showed no significant expression of AMBN. Overexpression of AMBN in osteogenic cultures induced no noticeable changes in mineralisation. In wild type mice, AMBN was immunodetected in ameloblasts and enamel, but not in normal bone, and at sites where bone remodelling and repair were induced. Bone remodelling during ETM and BDT repair in AMBNΔ5-6 mice were not significantly different from that in wild type animals. Our results suggest that AMBN does not influence osteogenic activity in vitro under the conditions used, and does not participate in craniofacial bone remodelling under mechanical stress and in repair of non-critical size bone defects.


Reinforcement of bond strength of self-etching orthodontic adhesive.

Abstract Objective: To determine the reinforcement of bond strength of a self-etching system by applying a pretreatment agent. Materials and Methods: Sixty extracted human premolars were used in this study. The enamel surfaces were treated with four pretreatment agents?phosphoric acid, polyacrylic acid, citric acid, and ammonium hexafluorosilicate (SiF)?and were examined under a scanning electron microscope. Afterward, orthodontic brackets were bonded with a self-etching adhesive system (n ?=? 10 for each agent), and shear bond strength was measured through a debonding process. The adhesive remnant index (ARI) was also assessed. Results: Enamel surfaces treated with polyacrylic acid seemed almost the same as intact enamel. Treatment with SiF induced slight shallow depressions compared with the intact enamel. On the other hand, enamel surfaces treated with citric acid and phosphoric acid showed severe etching patterns. All pretreatments increased the bond strength, but SiF-treated specimens revealed the greatest strength (12.201 ? 1.048?MPa), followed by polyacrylic acid (12.030 ? 2.103?MPa). The control group with no pretreatment showed the least strength (9.078 ? 1.678?MPa). All pretreatments increased ARI score compared with the control group. Conclusions: Surface conditioning before bracket adhesion could reinforce the bond strength of the self-etching adhesive system, resulting in a more reliable bonding system.


Application of Temporary Anchorage Devices for the Treatment of Adult Class III Malocclusions


Ultrasound stimulation attenuates root resorption of rat replanted molars and impairs tumor necrosis factor- signaling in vitro.

Rego EB, Inubushi T, Miyauchi M, Kawazoe A, Tanaka E, Takata T, Tanne K. Ultrasound stimulation attenuates root resorption of rat replanted molars and impairs tumor necrosis factor-α signaling in vitro. J Periodont Res 2011; 46: 648-654. © 2011 John Wiley & Sons A/S. Background and Objective: A therapeutic protocol to minimize root resorption induced by tooth replantation has not yet been universally established. In this context, noninvasive modality such as ultrasound therapy have been a focus of increased interest. This study aimed to evaluate the inhibitory effect of ultrasound therapy on root resorption of replanted rat molars. In addition, the study aimed to promote insights into the mechanism through which ultrasound mediates the metabolism of periodontal cells in vitro. Material and Methods: An experimental model of tooth replantation in rats, involving luxation and immediate replacement of the maxillary first molars, was used to assess the inhibitory effect of an ultrasound-therapy regimen (15 min of exposure to ultrasound, each day for 21 d) on root resorption. Moreover, the effect of ultrasound on osteoclastogenesis/cementoclastogenesis was examined in vitro using a mouse osteoblastic stromal cell line (ST2) and a mouse cementoblastic cell line (OCCM-30). Results: The area of root resorption lacunae was statistically decreased (p < 0.01) in the ultrasound-treated sample. In addition, immunohistochemical staining, using murine TNF-α polyclonal antibody, failed to detect tumor necrosis factor-α (TNF-α) protein in the ultrasound-treated sample compared with the control. An in vitro study showed that the lipopolysaccharide (LPS)-induced expression of Tnfalpha mRNA was significantly reduced by ultrasound therapy in both osteoblastic and cementoblastic cells. Moreover, the TNF-α-induced up-regulation of Rankl mRNA was also inhibited by ultrasound. Conclusion: Ultrasound may contribute to the reduction of the trauma-induced inflammatory reaction through impairment of the TNF-α signaling pathway. It is therefore suggested that ultrasound shows potential as a therapeutic tool to optimize the regenerative potential of periodontal tissues on replanted teeth.


Superficial zone protein affects boundary lubrication on the surface of mandibular condylar cartilage

We examined the localization and boundary lubricating function of superficial zone protein (SZP) on the surface of mandibular condylar cartilage. Chondrocytes were separated from the surface layer of mandibular condylar cartilage of 6- to 9-month-old female pigs. A cyclic tensile strain of 7% or 21% cell elongation was applied to the cultured chondrocytes. Gene expression levels of cartilage matrix proteins and secretory phospholipase A(2) (sPLA(2)) were quantified by real-time polymerase chain reaction analysis. The friction coefficient of the mandibular condylar surface was measured by a friction tester before and after treatment with 0.1 U/ml sPLA(2). Significantly higher mRNA levels of SZP and type I collagen were found in chondrocytes from the superficial layer than in those in the other layers. The SZP mRNA level was up-regulated by cyclic tensile strain of 7% and 21% cell elongation. Cyclic tensile strain of 21% cell elongation up-regulated the sPLA(2) mRNA level. The friction coefficient of the condylar surface was increased significantly by treatment with sPLA(2). The removal of SZP from the surface layer of mandibular condylar cartilage by sPLA(2) resulted in a significant increase in the friction coefficient on the surface of articular cartilage.


Atelocollagen-mediated systemic administration of myostatin-targeting siRNA improves muscular atrophy in caveolin-3-deficient mice.

Small interfering RNA (siRNA)-mediated silencing of gene expression is rapidly becoming a powerful tool for molecular therapy. However, the rapid degradation of siRNAs and their limited duration of activity require efficient delivery methods. Atelocollagen (ATCOL)-mediated administration of siRNAs is a promising approach to disease treatment, including muscular atrophy. Herein, we report that ATCOL-mediated systemic administration of a myostatin-targeting siRNA into a caveolin-3-deficient mouse model of limb-girdle muscular dystrophy 1C (LGMD1C) induced a marked increase in muscle mass and a significant recovery of contractile force. These results provide evidence that ATCOL-mediated systemic administration of siRNAs may be a powerful therapeutic tool for disease treatment, including muscular atrophy.


Efficient usage of implant anchorage in treatment of overerupted maxillary first molar and mesially inclined mandibular molars

This case report demonstrates the efficient use of implant anchorage in a patient with mesially inclined mandibular molars and an overerupted maxillary molar. A 14-year-old girl had an overerupted maxillary right first molar, possibly because of severely inclined mandibular right molars. Two-step use of miniplate anchorage in the right zygomatic process was proposed. As the first step, the overerupted maxillary first molar was intruded with elastic chains from the miniplate for 10 months. Then the maxillary right molars were distalized by using the miniplate to correct the Class II molar relationship. In the mandible, the first molar was extruded with intermaxillary elastics applied from the miniplate to the molar for 7 months after the uprighting of the mandibular right second molar. The results suggest that the use of 2-step implant anchorage is efficient for intrusion and distalization of maxillary molars and extrusion and uprighting of mandibular inclined molars.

American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO)


顎関節症患者に対する矯正歯科治療ー長期経過例ー

顎関節症患者に対する矯正歯科治療ー長期経過例ー

日本成人矯正歯科学会雑誌

日本成人矯正歯科学会雑誌


The expression of TGF-β3 for epithelial-mesenchyme transdifferentiated MEE in palatogenesis.

The fate of the palatal medial edge epithelial (MEE) cells undergoes programming cell death, migration, and epithelial-mesenchymal transdifferentiation (EMT) coincident with the process of palatal fusion and disappearance of MEE. Mesenchymal cells in the palate have both cranial neural crest (CNC) and non-CNC origins. The objectives of this study were to identify the populations of palatal mesenchymal cells using β-galactosidase (β-gal) and DiI cell lineage markers, and to determine whether MEE-derived cells continued to express transforming growth factor-β3 (TGF-β3) and transforming growth factor-β type III receptor (TβR-III), which were specific for MEE. A model has been developed using Wnt1 tissue specific expression of Cre-recombinase to activate β-gal solely in the CNC. The expressions of TGF-β3 and TβR-III in MEE were temporally correlated with critical events in palatogenesis. Three cell populations could be distinguished in the palatal mesenchymal CNC-derived, non-CNC derived and MEE-derived. After fusion, β-gal- and DiI+ mesenchymal cells continued to express TGF-β3, however TβR-III was expressed only in the epithelial MEE, as well as keratin expression. In addition, we performed laser capture microdissection to identify mRNA expression of isolated DiI+ MEE cells. Both epithelial and transdifferentiated MEE have expressed TGF-β3, however, TβR-III was only expressed in epithelium. Extracellular matrix, especially MMP13 has been expressed coincident with fused stage which can be strongly associated with TGF-β3. These results demonstrate that combining a heritable marker and a cell lineage dye can distinguish different populations of mesenchymal cells in the developing palate. Furthermore, TGF-β3 and MMP13 could be strongly associated with EMT in palatogenesis.


Effects of low-intensity pulsed ultrasound on the expression and activity of hyaluronan synthase and hyaluronidase in IL-1β-stimulated synovial cells.

The purpose of this study is to examine effects of low-intensity pulsed ultrasound (LIPUS) on metabolism of hyaluronan (HA) in synovial membrane cells stimulated by IL-1β. Rabbit knee synovial membrane cell line, HIG-82, was cultured in medium with the presence or absence of 1 ng/mL IL-1β, and after 4 h the cell was exposed to LIPUS for 15 min. The mRNA levels of HA synthase (HAS) 2,3, hyaluronidase (HYAL) 2, and cyclooxygenase (COX)-2 were examined by real-time PCR analysis. Concentrations of HA and PGE2 were quantified by use of enzyme linked immunosorbent assay (ELISA). The COX-2 level was analyzed by western blotting. Gene levels of HAS2 and HAS3 in IL-1β-stimulated cells were up-regulated significantly (p < 0.01) by LIPUS. HYAL2 mRNA was up-regulated by the treatment with IL-1β, whereas down-regulated significantly (p < 0.01) by the following LIPUS exposure. Furthermore, IL-1β stimulation enhanced COX-2 and PGE2 expression as compared to the untreated control, and IL-1β-induced COX-2 and PGE2 expression was inhibited by LIPUS. These results suggest that LIPUS enhanced HA synthesis and inhibited HYAL2 expression, leading to the accumulation of high-molecular weight HA. Therefore, LIPUS stimulation may be a better candidate as medical remedy to treat inflammatory joint diseases accompanied with HA degradation in synovial fluid.


Three-dimensional finite element analysis of cartilaginous tissues in human temporomandibular joint during prolonged clenching.

OBJECTIVE: Bruxism, the parafunctional habit of nocturnal grinding of the teeth and clenching, is associated with the onset of joint degeneration. Especially prolonged clenching is suggested to cause functional overloading in the temporomandibular joint (TMJ). In this study, the distributions of stresses in the cartilaginous TMJ disc and articular cartilage, were analysed during prolonged clenching. The purpose of this study was to examine if joint degradation due to prolonged clenching can be attributed to changes in stress concentration in the cartilaginous tissues. DESIGN: Finite element model was developed on the basis of magnetic resonance images from a healthy volunteer. Condylar movements recorded during prolonged clenching were used as the loading condition for stress analysis. RESULTS: At the onset of clenching (time=0s), the highest von Mises stresses were located in the middle and posterior areas (6.18MPa) of the inferior disc surface facing the condylar cartilage. The largest magnitude of the minimum principal stress (-6.72MPa) was found in the condylar cartilage. The stress concentrations were relieved towards the superior disc surface facing the temporal cartilage. On the surfaces of the temporal cartilage, relatively lower stresses were found. After 5-min clenching, both stress values induced in the TMJ components were reduced to 50-80% of the stress values at the onset of clenching, although the concomitant strains increased slightly during this period. CONCLUSIONS: It is suggested that both the condylar and temporal cartilage layers along with the TMJ disc, play an important role in stress distribution and transmission during prolonged clenching due to tissue expansion. Furthermore, our study suggests that a development of stress concentrations in the TMJ during prolonged clenching and risk factors for the initiation of TMJ degeneration could not be confirmed.


Delivery of small interfering RNA with a synthetic collagen poly(Pro-Hyp-Gly) for gene silencing in vitro and in vivo.

Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro-Hyp-Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long-term gene silencing in vivo. We found that the SYCOL-mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti-luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL-based non-viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro.


Severity of alveolar cleft affects prognosis of infant orthopedics in complete unilateral cleft lip and palate: three-dimensional evaluation from cheiloplasty to palatoplasty.

The purpose of this study was to investigate the relationships between severity of alveolar cleft and treatment outcome of infant orthopedics in patients affected by complete unilateral cleft lip and palate from cheiloplasty to palatoplasty with a three-dimensional evaluation method. Treatment outcomes of infant orthopedics were evaluated using three-dimensional linear and angular measurements of plaster models after cheiloplasty (T1) and before palatoplasty (T2). Eleven patients who had a width of alveolar cleft (WC) less than 4.0 mm at T1 (mild group) and 13 patients who had a WC 4.0 mm or greater (severe group) were compared and analyzed. From T1 to T2, the lengths of the alveolar segments were increased, and the WC was decreased without palatal collapse of alveolar segments in both groups. However, the WC in the severe group was significantly decreased by increased growth of the major segment compared with the mild group. The incisive papilla had a more evoked growth to the alveolar cleft side than in the severe group. Conclusively, infant orthopedics was quite useful in reducing WC in patients affected by unilateral cleft lip and palate after cheiloplasty, and the severity of WC significantly affected the prognosis of infant orthopedics.


RNA干渉法による治療を実現するための研究

RNA干渉法による治療を実現するための研究

The Journal of Chu-Shikoku Orthodontic Society

中·四国矯正歯科学会雑誌


顎顔面成長に対する咀嚼の重要性

顎顔面成長に対する咀嚼の重要性

中·四国矯正歯科学会雑誌


A comprehensive treatment case of severe deep bite with oligodontia

Oligodontiaを伴う著しい過蓋咬合に対する包括的治療例

中·四国矯正歯科学会雑誌


A case of maxillofacial saggital fracture reducted by a reverse-activated rapid palatal expander

顔面骨骨折による咬合不全に対し，急速拡大装置を逆回転することで整復した1症例

中·四国矯正歯科学会雑誌


Two cases of Angle Class II division 1 malocclusion treated with dynamic positioner with facebow

Dynamic positioner with facebowを用いて治療を行ったアングルⅡ級1類の2症例

中·四国矯正歯科学会雑誌


The relationship between the basal arch width of maxilla and the hearing level

上顎歯槽基底弓幅径と聴力との関係