Role of FGF/FGFR signaling in skeletal development and homeostasis: learning from mouse models

Fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling plays essential roles in bone development and diseases. Missense mutations in FGFs and FGFRs in humans can cause various congenital bone diseases, including chondrodysplasia syndromes, craniosynostosis syndromes and syndromes with dysregulated phosphate metabolism. FGF/FGFR signaling is also an important pathway involved in the maintenance of adult bone homeostasis. Multiple kinds of mouse models, mimicking human skeleton diseases caused by missense mutations in FGFs and FGFRs, have been established by knock-in/out and transgenic technologies. These genetically modified mice provide good models for studying the role of FGF/FGFR signaling in skeleton development and homeostasis. In this review, we summarize the mouse models of FGF signaling-related skeleton diseases and recent progresses regarding the molecular mechanisms, underlying the role of FGFs/FGFRs in the regulation of bone development and homeostasis. This review also provides a perspective view on future works to explore the roles of FGF signaling in skeletal development and homeostasis. Mouse models are revealing new insights into the roles of fibroblast growth factor (FGF) in human bone development and skeletal diseases. In a review article, Lin Chen and colleagues from the Third Military Medical University in Chongqing, China, highlight the many essential roles that FGFs, a family of growth factors, and their receptors play in the formation of a healthy skeleton. Mutations in FGF-associated genes can cause a range of congenital bone disorders. The authors discuss the ways in which scientists are genetically engineering mice to harbor mutations in a range of genes coding for FGFs and their receptors. These animal models are offering a window into the molecular mechanisms that underlie genetic skeletal diseases and providing attractive drug targets for treating many bone-related disorders.