Deletion of FGFR3 in Osteoclast Lineage Cells Results in Increased Bone Mass in Mice by Inhibiting Osteoclastic Bone Resorption
Deletion of FGFR3 in Osteoclast Lineage Cells Results in Increased Bone Mass in Mice by Inhibiting Osteoclastic Bone Resorption
复制标题
破骨细胞谱系细胞中 FGFR3 的缺失通过抑制破骨细胞骨吸收导致小鼠骨量增加
DOI：
10.1002/jbmr.2839
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发表时间：
2016-09-01
影响因子：
6.2
通讯作者：
Chen, Lin
中科院分区：
文献类型：
--
作者：
Su, Nan;Li, Xiaogang;Chen, Lin
成纤维细胞生长因子受体 3 (FGFR3) 参与骨重塑。 Fgfr3 整体敲除和激活小鼠均表现出骨量减少，破骨细胞形成或骨吸收活性增加。为了阐明FGFR3对破骨细胞的直接影响，我们特意删除了破骨细胞谱系细胞中的Fgfr3。破骨细胞谱系细胞中 Fgfr3 缺陷（突变体 [MUT]）的成年小鼠表现出骨量增加。在钻孔缺损模型中，MUT 小鼠皮质骨钻孔区域的骨重塑也因残余编织骨吸收延迟而受损。体外测定表明，野生型和 Fgfr3 缺陷型骨髓单核细胞来源的抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞的数量没有显着差异，表明 FGFR3 对破骨细胞形成没有显着影响。 Fgfr3缺陷的破骨细胞的骨吸收活性显着降低，伴随着Trap、Ctsk和Mmp 9表达的下调。体外FGF2上调的破骨细胞骨吸收活性在Fgfr3缺陷的破骨细胞中也受到损害，表明FGFR3可能参与了FGF2对破骨细胞骨吸收活性的调节。 Fgfr3 缺乏的破骨细胞粘附减少但迁移减少可能是骨吸收活性受损的原因。我们的研究首次从遗传学角度表明FGFR3对破骨细胞骨吸收的直接正向调节。 © 2016 美国骨与矿物质研究学会。
Fibroblast growth factor receptor 3 (FGFR3) participates in bone remodeling. Both Fgfr3 global knockout and activated mice showed decreased bone mass with increased osteoclast formation or bone resorption activity. To clarify the direct effect of FGFR3 on osteoclasts, we specifically deleted Fgfr3 in osteoclast lineage cells. Adult mice with Fgfr3 deficiency in osteoclast lineage cells (mutant [MUT]) showed increased bone mass. In a drilled‐hole defect model, the bone remodeling of the holed area in cortical bone was also impaired with delayed resorption of residual woven bone in MUT mice. In vitro assay demonstrated that there was no significant difference between the number of tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclasts derived from wild‐type and Fgfr3‐deficient bone marrow monocytes, suggesting that FGFR3 had no remarkable effect on osteoclast formation. The bone resorption activity of Fgfr3‐deficient osteoclasts was markedly decreased accompanying with downregulated expressions of Trap, Ctsk, and Mmp 9. The upregulated activity of osteoclastic bone resorption by FGF2 in vitro was also impaired in Fgfr3‐deficient osteoclasts, indicating that FGFR3 may participate in the regulation of bone resorption activity of osteoclasts by FGF2. Reduced adhesion but not migration in osteoclasts with Fgfr3 deficiency may be responsible for the impaired bone resorption activity. Our study for the first time genetically shows the direct positive regulation of FGFR3 on osteoclastic bone resorption. © 2016 American Society for Bone and Mineral Research.