Involvement of receptor-interacting protein 140 in estrogen-mediated osteoclasts differentiation, apoptosis, and bone resorption
Involvement of receptor-interacting protein 140 in estrogen-mediated osteoclasts differentiation, apoptosis, and bone resorption
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DOI：
10.1007/s12576-016-0447-2
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发表时间：
2017-01-01
影响因子：
2.3
通讯作者：
Zhao, Yan
中科院分区：
文献类型：
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作者：
Piao, Hongying;Chu, Xiaojie;Zhao, Yan
绝经后雌激素的撤退导致破骨细胞形成和骨吸收增加，这是绝经后骨质疏松症最重要的机制之一。最近，越来越多的证据表明受体相互作用蛋白 140 与雌激素调节的代谢疾病有关，包括脂肪代谢和脂质代谢。然而，关于受体相互作用蛋白140在雌激素调节骨代谢中的作用知之甚少。在本研究中，蛋白质印迹揭示雌激素使破骨细胞中受体相互作用蛋白140的表达显着增加，但在成骨细胞和骨髓间充质干细胞中则没有。此外，TRAP染色和骨吸收测定分析表明，受体相互作用蛋白140的消耗可以显着减轻雌激素对破骨细胞形成和骨吸收活性的抑制作用。此外，雌激素可以通过Fas/FasL途径增加受体相互作用蛋白140的表达，从而诱导破骨细胞凋亡。总而言之，受体相互作用蛋白 140 可能是雌激素介导的破骨细胞生成和骨吸收的关键参与者。
Estrogen withdrawal following menopause results in an increase of osteoclasts formation and bone resorption, which is one of the most important mechanisms of postmenopausal osteoporosis. Recently, growing evidence has suggested that receptor-interacting protein 140 was implicated in estrogen-regulated metabolic disease, including fat metabolism and lipid metabolism. However, little is known regarding the role of receptor-interacting protein 140 in the regulation of bone metabolic by estrogen. In the present study, Western blotting disclosed that estrogen brings a significant increasing expression of receptor-interacting protein 140 in osteoclasts, but not in osteoblasts and bone marrow mesenchymal stem cells. Furthermore, analysis of TRAP staining and bone resorption assay showed that depletion of receptor-interacting protein 140 could significantly alleviate the inhibitory effects of estrogen on osteoclasts formation and bone resorption activity. Moreover, estrogen could induce osteoclasts apoptosis by increasing receptor-interacting protein 140 expression through the Fas/FasL pathway. Taken together, receptor-interacting protein 140 might be a critical player in estrogen-mediated osteoclastogenesis and bone resorption.