Gain-of-function mutation of FGFR3 results in impaired fracture healing due to inhibition of chondrocyte differentiation.
Fracture healing is a complicated regeneration process which to some extent recapitulates bone development. Fibroblast growth factor receptor 3 (FGFR3) has a negative regulatory effect on endochondral ossification, and FGFR3 is also expressed in prehypertrophic and hypertrophic chondrocytes during fracture healing. However, the actual role of FGFR3 during bone regeneration is not fully understood. Therefore we investigated the role of FGFR3 in fracture repair using a non-stabilized fracture model. Fracture repair in gain-of-function mutation of FGFR3 (Fgfr3(G369C/+)) mice was delayed, with more cartilage callus on day 14 and residue of cartilage in the callus on day 21. Histologic, in-situ hybridization and qRT-PCR analysis showed that differentiation of mesenchymal cells into chondrocytes and hypertrophic differentiation was delayed in Fgfr3(G369C/+) mice during fracture healing. These results indicated that activating mutation of FGFR3 could lead to impaired bone repair due to inhibition of chondrocyte differentiation.
Su
Nan
N
State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Yang
Jing
J
Xie
Yixia
Y
Du
Xiaolan
X
Lu
Xiumin
X
Yin
Zhiyong
Z
Yin
Liangjun
L
Qi
Huabing
H
Zhao
Ling
L
Feng
Jianquan
J
Chen
Lin
L
D000818:Animals; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000166:cytology / Q000201:enzymology; D002356:Cartilage / Q000166:cytology / Q000201:enzymology; D002454:Cell Differentiation / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology* / Q000201:enzymology; D017102:Fracture Healing / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*
C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3