MiR-503 Regulates Osteoclastogenesis via Targeting RANK
MiR-503 Regulates Osteoclastogenesis via Targeting RANK
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DOI：
10.1002/jbmr.2032
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发表时间：
2014-02-01
影响因子：
6.2
通讯作者：
Luo, Xiang-Hang
中科院分区：
文献类型：
--
作者：
Chen, Chao;Cheng, Peng;Luo, Xiang-Hang
MicroRNAs （miRNAs）在破骨细胞发生和骨吸收中起重要作用。然而，没有研究调查miRNA在绝经后骨质疏松症中的作用。在这里，我们报道，与绝经后健康女性相比，绝经后骨质疏松症患者的破骨细胞- cd14（+）外周血单核细胞（PBMCs）循环祖细胞中的miR-503明显降低。在CD14(+) PBMCs中过表达miR-503抑制核因子- b配体受体激活剂（RANKL）诱导的破骨细胞发生。相反，CD14(+) PBMCs中miR-503的沉默促进了破骨细胞的发生。RANK通过与RANKL结合激活，诱导破骨细胞分化，被证实是miR-503的靶点。在体内，在卵巢切除（OVX）小鼠中，使用特异性安塔戈米尔沉默miR-503可增加RANK蛋白表达，促进骨吸收，减少骨量，而在OVX小鼠中，使用阿戈米尔过表达miR-503可抑制骨吸收并防止骨质流失。因此，我们的研究揭示了miR-503在绝经后骨质疏松的发病机制中起着重要作用，为骨质疏松的治疗提供了新的途径。(c) 2014年美国骨与矿物研究学会。
MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. However, no study has investigated the role of miRNA in postmenopausal osteoporosis. Here, we report that miR-503 was markedly reduced in circulating progenitors of osteoclasts-CD14(+) peripheral blood mononuclear cells (PBMCs) from postmenopausal osteoporosis patients compared with those from postmenopausal healthy women. Overexpression of miR-503 in CD14(+) PBMCs inhibited receptor activator of nuclear factor-B ligand (RANKL)-induced osteoclastogenesis. Conversely, silencing of miR-503 in CD14(+) PBMCs promoted osteoclastogenesis. RANK, which is activated by the binding of RANKL and inducing osteoclast differentiation, was confirmed to be a target of miR-503. In vivo, silencing of miR-503 using a specific antagomir in ovariectomy (OVX) mice increased RANK protein expression, promoted bone resorption, and decreased bone mass, whereas overexpression of miR-503 with agomir inhibited bone resorption and prevented bone loss in OVX mice. Thus, our study revealed that miR-503 plays an important role in the pathogenesis of postmenopausal osteoporosis and contributes to a new therapeutic way for osteoporosis. (c) 2014 American Society for Bone and Mineral Research.