Spatial and temporal gene expression for fibroblast growth factor type I receptor (FGFR1) during fracture healing in the rat

Recent experiments have shown that exogenous basic fibroblast growth factor (bFGF) enlarges fracture callus and accelerates the healing of osteotomize d long bones. The actions of bFGF are mediated by four different transmembr ane receptors (FGFR1-4). Among them, FGFR1 has a high affinity for bFGF, an d gain-of-function mutations of the FGFR1 gene cause craniosynostosis in hu mans. Gene expression for FGFRI has been analyzed in embryogenesis-1 howeve r, in skeletal repair, detailed expression of FGFRI has not been fully esta blished. In the present study, a rat model of closed femoral fracture heali ng was used to quantify mRNA encoding the FGFRI and to characterize cells e xpressing FGFRI by in situ hybridization. Gene expression for FGFRI was rap idly upregulated after fracture; its mRNA level on day 1 was 3.4-fold highe r than that of unfractured femora. At this stage, a moderate signal for FGF R1 was detected in periosteal osteoprogenitor cells, inflammatory cells nea r fracture sites, and cells among muscle layers. FGFR1 MRNA reached peak ex pression when callus remodeling actively progressed (6.8-fold on day 14), a nd remained elevated even in the later stages of healing (6.3-fold on day 2 8). During the intermediate stage of fracture healing, a strong signal for FGFR1 was diffusely distributed in mature osteoblasts in the hard callus, a nd mature osteoclasts also expressed a weak signal for FGFRI. These results suggest that FGF/FGFR1 signaling has multifunctional roles during fracture healing and may regulate both osteoblasts and osteoclasts, contributing to bone formation and callus remodeling. (C) 2001 by Elsevier Science Inc. Al l rights reserved.