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Chondrocyte FGFR3 regulates bone mass by inhibiting osteogenesis

Research paper by Xuan Wen, Xiaogang Li, Yubing Tang, Junzhou Tang, Siru Zhou, Yangli Xie, Jingyuan Guo, Jing Yang, Xiaolan Du, Nan Su, Lin Chen

Indexed on: 12 Oct '16Published on: 11 Oct '16Published in: Journal of Biological Chemistry



Abstract

Chondrogenesis can regulate bone formation. Fibroblast growth factor receptor 3, highly expressed in chondrocytes, is a negative regulator of bone growth. To investigate whether chondrocyte FGFR3 regulates osteogenesis, thereby contributing to postnatal bone formation and bone remodeling, mice with conditional knockout of Fgfr3 in chondrocytes (mutant, MUT) were generated. MUT mice displayed overgrowth of bone with lengthened growth plates. Bone mass of MUT mice was significantly increased at both 1 and 4 months of age. Histological analysis showed that osteoblast number and bone formation were remarkably enhanced after deletion of Fgfr3 in chondrocytes. Chondrocyte-osteoblast co-culture assay further revealed that Fgfr3 deficiency in chondrocytes promoted differentiation and mineralization of osteoblasts by up-regulating the expressions of Ihh, BMP 2, 4 and 7, and down-regulating Noggin expression. In addition, osteoclastogenesis was also impaired in MUT mice with decreased osteoclast number lining trabecular bone, which may be related to the reduced ratio of Rankl to Opg in Fgfr3 deficient chondrocytes. This study reveals that chondrocyte FGFR3 is involved in the regulation of bone formation and bone remodeling by a paracrine mechanism.