Abstract
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.