TRPV6 is a potential regulator of bone resorption in bone loss induced by estrogen deficiency

Jun Ma; Jiajia Lu; Zhibin Zhou; Nan Lu; Jia He; Lei Zhu; Tianwen Ye

doi:10.1016/j.isci.2021.103261

TRPV6 is a potential regulator of bone resorption in bone loss induced by estrogen deficiency

iScience. 2021 Oct 12;24(11):103261. doi: 10.1016/j.isci.2021.103261. eCollection 2021 Nov 19.

Authors

Jun Ma^{1

2}, Jiajia Lu¹, Zhibin Zhou³, Nan Lu¹, Jia He², Lei Zhu¹, Tianwen Ye¹

Affiliations

¹ Department of Orthopedic, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, China.
² Department of Health Statistics, Naval Medical University, 800 Xiangyin Road, Shanghai, China.
³ Department of Orthopedic Surgery, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenyang 110016, China.

Abstract

The precise effect of estrogen (E2) on osteoclast function is still poorly understood. The aim of this study was to investigate the potential role of transient receptor potential vanilloid 6 (TRPV6) in E2-mediated osteoclast function and to characterize the relevant underlying mechanisms. Here, we found that Trpv6 is drastically decreased in ovariectomy operation animals and the administration of E2 results in an increased expression of Trpv6 in osteoclasts. In contrast, Trpv6 depletion significantly blocked the inhibitory effects of E2 on bone resorption activity, and silencing Trpv6 alleviated E2-induced osteoclast apoptosis. In addition, we found that E2 regulates the transcription of Trpv6 through ERα, by interacting with C/EBPβ and NF-κB. Chip assay analysis indicated that C/EBPβ regulates Trpv6 transcription by binding to Trpv6 promoter fragments -1,866 nt to -1,761 nt and -2,685 nt to -2,580 nt, whereas NF-κB binds to the -953 nt to -851 nt region. We conclude that TRPV6 has a significant effect on E2-mediated osteoclast function.

Keywords: Developmental biology; Endocrinology; Molecular biology.