Int J Biol Sci 2017; 13(8):1029-1037. doi:10.7150/ijbs.19309
FGFR3 deficient mice have accelerated fracture repair
Department of Rehabilitation Medicine, Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
* Yangli Xie and Fengtao Luo contributed equally to this work.
Xie Y, Luo F, Xu W, Wang Z, Sun X, Xu M, Huang J, Zhang D, Tan Q, Chen B, Jiang W, Du X, Chen L. FGFR3 deficient mice have accelerated fracture repair. Int J Biol Sci 2017; 13(8):1029-1037. doi:10.7150/ijbs.19309. Available from http://www.ijbs.com/v13p1029.htm
Bone fracture healing is processed through multiple biological stages that partly recapitulates the skeletal development process. FGFR3 is a negative regulator of chondrogenesis during embryonic stage and plays an important role in both chondrogenesis and osteogenesis. We have investigated the role of FGFR3 in fracture healing using unstabilized fracture model and found that gain-of-function mutation of FGFR3 inhibits the initiation of chondrogenesis during cartilage callus formation. Here, we created closed, stabilized proximal tibia fractures with an intramedullary pin in Fgfr3-/-mice and their littermate wild-type mice. Fracture healing was evaluated by radiography, micro-CT, histology, and real-time polymerase chain reaction (RT-PCR) analysis. The fractured Fgfr3-/- mice had increased formation of cartilaginous callus, more fracture callus, and more rapid endochondral ossification in fracture sites with up-regulated expressions of chondrogenesis related gene. The fractures of Fgfr3-/- mice healed faster with accelerated fracture callus mineralization and up-regulated expression of osteoblastogenic genes. The healing of fractures in Fgfr3-/- mice was accelerated in the stage of formation of cartilage and endochondral ossification. Downregulation of FGFR3 activity can be considered as a potential bio-therapeutic strategy for fracture treatment.
Keywords: FGFR3, fracture treatment