NFI-C Is Required for Epiphyseal Chondrocyte Proliferation during Postnatal Cartilage Development

Stringent regulation of the chondrocyte cell cycle is required for endochondral bone formation. During the longitudinal growth of long bones, mesenchymal stem cells condense and differentiate into chondrocytes. Epiphyseal chondrocytes sequentially differentiate to form growth- plate cartilage, which is subsequently replaced with bone. Although the importance of nuclear factor 1C (Nfic) in hard tissue formation has been extensively studied, knowledge regarding its biological roles and molecular mechanisms in this process remains insufficient. Herein, we demonstrated that Nfic deficiency affects femoral growth-plate formation. Chondrocyte proliferation was downregulated and the number of apoptotic cell was increased in the growth plates of Nfic^-/- mice. Further, the expression of the cell cycle inhibitor p21 was upregulated in the primary chondrocytes of Nfic^-/- mice, whereas that of cyclin D1 was downregulated. Our findings suggest that Nfic may contribute to postnatal chondrocyte proliferation by inhibiting p21 expression and by increasing the stability of cyclin D1 protein.