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This version published online on July 3, 2003
Endocrinology, doi:10.1210/en.2003-0158
A more recent version of this article appeared on October 1, 2003
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Submitted on January 31, 2003
Accepted on June 26, 2003

Expression of Fibroblast Growth Factor Receptor-3 (FGFR3), Signal Transducer and Activator of Transcription-1 (STAT1), and Cyclin Dependent Kinase Inhibitor p21 During Endochondral Ossification: Differential Role of FGFR3 in Skeletal Development and Fracture Repair

Arata Nakajima1*, Sumito Shimizu1, Hideshige Moriya1, and Masashi Yamazaki1

1 Department of Orthopaedic Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan

* To whom correspondence should be addressed. E-mail: 98md0509{at}insei.m.chiba-u.ac.jp.

Increasing evidence suggests that FGFR3 is a negative regulator of endochondral bone growth; however, its role during skeletal repair is unknown. Using a rat model of closed femoral fracture healing, we analyzed the spatial and temporal expression of FGFR3. To assess a possible role for FGFR3 during healing, we also analyzed the spatial and temporal expression of STAT1 and cycline dependent kinase (CDK) inhibitor p21, important mediators of FGFR3 signaling. Before these experiments, we studied the spatial expression of FGFR3 during skeletal development in mouse embryos. At 16.5 and 19.5 days post coitum (p.c.), FGFR3 mRNA was strongly expressed in resting and proliferating chondrocytes, but weakly in hypertrophic chondrocytes and not in osteoblasts. In contrast, during fracture repair, it was strongly expressed in pre-hypertrophic chondrocytes, and the expression level reached a maximum on Day 14. Immunoreactivity for STAT1 was detected in the cytoplasm of chondrocytes on Days 4 and 7, while both in the cytoplasm and in the nucleus of hypertrophic chondrocytes on Day 14. Furthermore, FGFR3, STAT1, and p21 exhibited a similar temporal expression profile, suggesting that FGFR3-mediated STAT1-p21 signaling plays a role in fracture repair. These results indicate a differential role of FGFR3 in skeletal development and fracture repair.


Key words: FGFR3 • STAT1 • p21 • skeletal development • fracture repair




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