Regulation of TRPV5 transcription and expression by E2/ERα signalling contributes to inhibition of osteoclastogenesis.
Regulation of TRPV5 transcription and expression by E2/ERα signalling contributes to inhibition of osteoclastogenesis.
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E2/ERα 信号传导调节 TRPV5 转录和表达有助于抑制破骨细胞生成
DOI：
10.1111/jcmm.13718
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发表时间：
2018-10
影响因子：
5.3
通讯作者：
Ye T
中科院分区：
文献类型：
--
作者：
Song T;Lin T;Ma J;Guo L;Zhang L;Zhou X;Ye T
雌激素（E2）缺乏导致破骨细胞形成和活性增加是绝经后骨质疏松症的重要病因。我们前期的研究表明，E2通过增加瞬时受体电位香草酸5（TRPV 5）通道的表达来抑制骨细胞骨吸收。然而，E2增加TRPV 5表达的确切机制尚未完全阐明。本研究采用Western blot、定量真实的-time PCR、抗酒石酸酸性磷酸酶染色、F-肌动蛋白环染色、染色质免疫沉淀和荧光素酶检测等方法，探讨E2诱导TRPV 5表达抑制破骨细胞生成的机制。结果表明，TRPV 5的沉默或过表达显著影响破骨细胞的分化和活性。TRPV 5基因的沉默明显减轻了E2抑制破骨细胞生成的作用，导致骨吸收增加。E2通过增加TRPV 5表达促进成熟破骨细胞凋亡。进一步的研究表明，E2通过雌激素受体α（ERα）与NF-κB的相互作用增加TRPV 5的表达，NF-κ B可以直接与TRPV 5启动子区的−286 nt ~ −277 nt片段结合。综上所述，我们得出结论，TRPV 5在E2介导的破骨细胞形成，骨吸收活性和破骨细胞凋亡中起主导作用。此外，NF-κB在E2-ERα刺激TRPV 5表达的转录激活中起重要作用。
The increasing of osteoclasts formation and activity because of oestrogen (E2) deficiency is very important in the aetiology of postmenopausal osteoporosis. Our previous studies showed that E2 inhibited osteoclastic bone resorption by increasing the expression of Transient Receptor Potential Vanilloid 5 (TRPV5) channel. However, the exact mechanism by which E2 increases TRPV5 expression is not fully elucidated. In this study, Western blot, quantitative real‐time PCR, tartrate‐resistant acid phosphatase staining, F‐actin ring staining, chromatin immunoprecipitation and luciferase assay were applied to explore the mechanisms that E2‐induced TRPV5 expression contributes to the inhibition of osteoclastogenesis. The results showed that silencing or overexpressing of TRPV5 significantly affected osteoclasts differentiation and activity. Silencing of TRPV5 obviously alleviated E2‐inhibited osteoclastogenesis, resulting in increasing of bone resorption. E2 stimulated mature osteoclasts apoptosis by increasing TRPV5 expression. Further studies showed that E2 increased TRPV5 expression through the interaction of the oestrogen receptor α (ERα) with NF‐κB, which could directly bind to the fragment of −286 nt ~ −277 nt in the promoter region of trpv5. Taken together, we conclude that TRPV5 plays a dominant effect in E2‐mediated osteoclasts formation, bone resorption activity and osteoclasts apoptosis. Furthermore, NF‐κB plays an important role in the transcriptional activation of E2‐ERα stimulated TRPV5 expression.
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