FGFR3的功能获得性突变由于抑制软骨细胞分化而导致骨折愈合受损。
Gain-of-function mutation of FGFR3 results in impaired fracture healing due to inhibition of chondrocyte differentiation.
作者信息
Su Nan, Yang Jing, Xie Yixia, Du Xiaolan, Lu Xiumin, Yin Zhiyong, Yin Liangjun, Qi Huabing, Zhao Ling, Feng Jianquan, Chen Lin
机构信息
State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
出版信息
Biochem Biophys Res Commun. 2008 Nov 21;376(3):454-9. doi: 10.1016/j.bbrc.2008.08.165. Epub 2008 Sep 24.
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.
骨折愈合是一个复杂的再生过程，在一定程度上重现了骨骼发育。成纤维细胞生长因子受体3（FGFR3）对软骨内成骨具有负调节作用，并且在骨折愈合过程中，FGFR3也在肥大前软骨细胞和肥大软骨细胞中表达。然而，FGFR3在骨再生过程中的实际作用尚未完全明确。因此，我们使用不稳定骨折模型研究了FGFR3在骨折修复中的作用。FGFR3功能获得性突变（Fgfr3(G369C/+)）小鼠的骨折修复延迟，在第14天有更多的软骨痂，在第21天痂内有软骨残留。组织学、原位杂交和qRT-PCR分析表明，在骨折愈合过程中，Fgfr3(G369C/+)小鼠间充质细胞向软骨细胞的分化以及肥大分化均延迟。这些结果表明，FGFR3的激活突变可因抑制软骨细胞分化而导致骨修复受损。
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