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Sirtuin 1 inhibits TNF-α-mediated osteoclastogenesis of bone marrow-derived macrophages through both ROS generation and TRPV1 activation

  • Shu Yan
  • Lujie Miao
  • Yahua Lu
  • Liangzhi Wang
Article
  • 83 Downloads

Abstract

Sirtuin 1 (SIRT1), also known as NAD-dependent deacetylase, has been reported to increase in vivo osteoclast-mediated bone resorption. However, its effects on osteoclastogenesis or bone loss in vitro have not been widely examined. Therefore, the effects and underlying mechanism of SIRT1 on osteoclast differentiation in mice in vitro were studied. During RANKL-induced osteoclastogenesis in differentiated bone marrow-derived macrophages (BMMs), SIRT1 downregulation was observed. The use of resveratrol (SIRT1 activator) and SIRT1 overexpression was found to inhibit osteoclastogenesis, which was confirmed by TRAP staining and activity loss, reduced expression of osteoclast markers and related genes, and a decrease in the number of multinuclear cells. In contrast, treatment with EX-527 (SIRT1 inhibitor) as well as SIRT1 silencing promoted osteoclastogenesis. Furthermore, the tumor necrosis factor (TNF)-α level was reduced by resveratrol treatment and SIRT1 overexpression but increased following EX-527 incubation and SIRT1 depletion. TNF-α silencing blocked the osteoclastogenesis of BMMs promoted by SIRT1 depletion. Moreover, transient receptor potential vanilloid 1 (TRPV1) channel activation and reactive oxygen species (ROS) production, which are associated with osteoclastogenesis, were impaired by TNF-α silencing. These data demonstrate that SIRT1 directly inhibits osteoclastogenesis by inhibiting ROS generation and TRPV1 channel activation under mediation of TNF-α.

Keywords

Osteoclastogenesis Bone marrow-derived macrophages Sirtuin 1 Tumor necrosis factor α Reactive oxygen species 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.General Medical WardsThe Third Affiliated Hospital of Soochow UniversityChangzhouChina
  2. 2.Department of GastroenterologyThe Third Affiliated Hospital of Soochow UniversityChangzhouChina

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