Fibroblast Growth Factor Receptor 3 Deficiency Does Not Impair the Osteoanabolic Action of Parathyroid Hormone on Mice.
Fibroblast Growth Factor Receptor 3 Deficiency Does Not Impair the Osteoanabolic Action of Parathyroid Hormone on Mice.
复制标题
成纤维细胞生长因子受体 3 缺陷不会损害甲状旁腺激素对小鼠的骨合成代谢作用
DOI：
10.7150/ijbs.14077
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发表时间：
2016
影响因子：
9.2
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Xie Y;Yi L;Weng T;Huang J;Luo F;Jiang W;Xian CJ;Du X;Chen L
总结：PTH通过促进成骨细胞的增殖和分化刺激Fgfr 3基因敲除小鼠的骨形成。简介：以往的研究表明，内源性成纤维细胞生长因子2（FGF-2）是所需的甲状旁腺激素（PTH）刺激骨合成的影响，然而，PTH刺激骨形成的确切机制和FGF受体介导这些行动的功能并不完全确定。成纤维细胞生长因子受体3（FGF receptor 3，FGFR 3）是骨代谢的重要调节因子，在软骨和骨发育过程中与甲状旁腺激素（PTH）/甲状旁腺激素受体（PTHrP）信号发生交叉作用。研究方法：分别于2月龄和4月龄对Fgfr 3基因敲除小鼠和野生型小鼠腹腔注射PTH，连续4周，然后采用双能X线吸收法（DEXA）、微计算机断层扫描（μCT）和骨组织形态计量学方法评价骨骼对PTH的反应。结果：间歇性PTH治疗可改善Fgfr 3-/-和野生型小鼠的骨密度（BMD）和股骨机械性能。组织形态计量学分析显示，PTH治疗后两种基因型的骨形成和骨吸收增加。PTH治疗增加了WT和Fgfr 3缺陷小鼠的松质骨体积（BV/TV）。Fgfr 3缺陷型和野生型骨中的合成代谢反应的特征在于PTH治疗后骨形成和吸收相关基因的增加。此外，我们发现，Fgfr 3 null成骨细胞（与野生型对照组相比）保持正常的能力，以应对PTH刺激的增殖，分化，成骨细胞标志物基因（Cbfa 1，骨桥蛋白和骨钙素）的表达增加，和Erk 1/2的磷酸化。结论：PTH的骨合成代谢作用不受FGFR 3缺乏的影响，这表明FGFR 3信号传导可能不是PTH活性的骨合成代谢作用所必需的。
Summary: PTH stimulates bone formation in Fgfr3 knockout mice through promotion of proliferation and differentiation in osteoblasts. Introduction: Previous studies showed that endogenous fibroblast growth factor 2 (FGF-2) is required for parathyroid hormone (PTH)-stimulated bone anabolic effects, however, the exact mechanisms by which PTH stimulate bone formation and the function of FGF receptors in mediating these actions are not fully defined. FGF receptor 3 (FGFR3) has been characterized as an important regulator of bone metabolism and is confirmed to cross-talk with PTH/PTHrP signal in cartilage and bone development. Methods: Fgfr3 knockout and wild-type mice at 2-month-old and 4-month-old were intraperitoneally injected with PTH intermittently for 4 weeks and then the skeletal responses to PTH were assessed by dual energy X-ray absorptiometry (DEXA), micro-computed tomography (μCT) and bone histomorphometry. Results: Intermittent PTH treatment improved bone mineral density (BMD) and femoral mechanical properties in both Fgfr3-/- and wild-type mice. Histomorphometric analysis showed that bone formation and bone resorption were increased in both genotypes following PTH treatment. PTH treatment increased trabecular bone volume (BV/TV) in WT and Fgfr3-deficient mice. The anabolic response in Fgfr3-deficient and wild-type bone is characterized by an increase of both bone formation and resorption-related genes following PTH treatment. In addition, we found that Fgfr3 null osteoblasts (compared to wild-type controls) maintained normal abilities to response to PTH-stimulated increase of proliferation, differentiation, expression of osteoblastic marker genes (Cbfa1, Osteopontin and Osteocalcin), and phosphorylation of Erk1/2. Conclusions: Bone anabolic effects of PTH were not impaired by the absence of FGFR3, suggesting that the FGFR3 signaling may not be required for osteoanabolic effects of PTH activities.