FGFR3 gain-of-function delays intramembranous bone healing in a mouse calvarial fracture model.

Fibroblast growth factor receptor 3 (FGFR3) is an important regulator of bone development and healing. Gain-of-function mutations in FGFR3 cause achondroplasia, the most common skeletal dysplasia characterized by short-limbed dwarfism. Our previous study showed that FGFR3 signaling accelerated bone repair through endochondral ossification during distraction osteogenesis. This study aimed to investigate the role of FGFR3 in intramembranous bone repair using a calvarial fracture model in gain-of-function transgenic Fgfr3 mice. Using micro-computed tomography, histomorphometric analysis, and real-time PCR, we found that Fgfr3 mice showed delayed bone healing, as evidenced by decreased bone mass, reduced callus formation, and suppressed numbers of osteoblasts and osteoclasts, along with downregulation of genes related to osteoblastogenesis and osteoclastogenesis. Additionally, in vitro assays using osteoblasts derived from calvarial bone demonstrated that FGFR3 activation impaired the osteogenic potential of osteoblasts. These findings indicate that FGFR3 acts as a negative regulator during intramembranous bone healing by inhibiting osteogenesis and affecting osteoclast-associated bone resorption. Our study provides insight into the mechanisms underlying fracture healing.