Yoshihiro Tamamura, Kei Sakamoto, Ken-Ichi Katsube and Akira Yamaguchi : Notch signaling is involved in Fgf23 upregulation in osteocytes., Biochemical and Biophysical Research Communications, 2019.
(要約)
Fgf23 acts as a phosphaturic factor secreted from osteocytes in bone, but the mechanism regulating Fgf23 is not fully understood. Here, we showed the colocalization of Fgf23, Notch, and Hes1, a downstream target of Notch signaling, in numerous osteocytes in cortical bone of femur in wild-type mice. We generated NICD (Notch intracellular domain)-transgenic mice driven by a 2.3 kb collagenα1 (I) (Col1a1) promoter fragment. Western blot and RT-PCR analyses revealed upregulation of Notch protein and mRNA levels in the bones of transgenic mice compared with those in wild-type mice. In the transgenic mice, immunohistochemical studies demonstrated that numerous osteocytes and osteoblasts express Notch in the rib, whereas only osteoblasts exhibit Notch in the femur. NICD-transgenic mice were characterized by upregulation of Fgf23 mRNA levels in the rib but not in the femur compared with that in wild type mice. These mice exhibited dwarfism associated with an osteomalacia phenotype. The expression of Alpl, Col1a1, and Bglap decreased in NICD-transgenic mice compared with wild-type mice. UMR-106 cells cultured on Jagged1-immobilized wells significantly increased Fgf23 expressions associating with upregulation of Hes1 and Hey1. These results imply that Notch signaling is a positive regulator for Fgf23 expression in osteocytes.
A Yamashita, Yoshihiro Tamamura, M Morioka, P Karagiannis, N Shima and N Tsumaki : Considerations in hiPSC-derived cartilage for articular cartilage repair, Inflammation and Regeneration, 38, 17, 1-7, 2018.
(要約)
A lack of cell or tissue sources hampers regenerative medicine for articular cartilage damage. We review and discuss the possible use of pluripotent stem cells as a new source for future clinical use. Human induced pluripotent stem cells (hiPSCs) have several advantages over human embryonic stem cells (hESCs). Methods for the generation of chondrocytes and cartilage from hiPSCs have been developed. To reduce the cost of this regenerative medicine, allogeneic transplantation is preferable. hiPSC-derived cartilage shows low immunogenicity like native cartilage, because the cartilage is avascular and chondrocytes are segregated by the extracellular matrix. In addition, we consider our experience with the aberrant deposition of lipofuscin or melanin on cartilage during the chondrogenic differentiation of hiPSCs. Cartilage generated from allogeneic hiPSC-derived cartilage can be used to repair articular cartilage damage.