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
Affiliations
Jun Ma
Department of Orthopedic, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, China; Department of Health Statistics, Naval Medical University, 800 Xiangyin Road, Shanghai, China
Jiajia Lu
Department of Orthopedic, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, China
Zhibin Zhou
Department of Orthopedic Surgery, General Hospital of Northern Theater Command, No.83, Wenhua Road, Shenyang 110016, China
Nan Lu
Department of Orthopedic, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, China
Jia He
Department of Health Statistics, Naval Medical University, 800 Xiangyin Road, Shanghai, China; Corresponding author
Lei Zhu
Department of Orthopedic, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, China; Corresponding author
Tianwen Ye
Department of Orthopedic, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Huangpu District, Shanghai, China; Corresponding author
Summary: 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.
