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Research Paper|Volume 11, Issue 19|pp 8103—8119

Disulfiram suppressed ethanol promoted RANKL-induced osteoclastogenesis in vitro and ethanol-induced osteoporosis in vivo via ALDH1A1-NFATc1 axis

Yewei Jia1,2, Jiawei Jiang3, Kangxian Zhao1, Tan Zhang1, Peng Sun1, Jiaxuan Peng4, Qichang Yang1, Yu Qian1
  • 1Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing), Zhejiang 312000, China
  • 2Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 312000, China
  • 3Department of Urinary Surgery, Jinhua Central Hospital (Jinhua Hospital, Zhejiang University School of Medicine, Jinhua), Zhejiang 321000, China
  • 4Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China
* Equal contribution
Received: July 29, 2019Accepted: September 5, 2019Published: October 8, 2019
https://doi.org/10.18632/aging.102279

Copyright © 2019 Jia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Excessive alcohol consumption is positively related to osteoporosis, and its treatment strategies are poorly developed. Disulfiram inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis; however, whether it can be used for ethanol-induced osteoclastogenesis and its underlying mechanism are still unclear. In this study, we demonstrated that ethanol promoted RANKL-induced osteoclast formation and bone resorption, whereas, disulfiram suppressed ethanol-induced osteoclastogenesis by abrogating the expression of nuclear factor of activated T cell c1 (NFATc1) in vitro. Further analysis revealed that aldehyde dehydrogenase 1A1 (ALDH1A1) is important for the expression of NFATc1, the master regulator of osteoclast differentiation. Furthermore, we showed that disulfiram protected ethanol-induced osteoporosis in vivo. Overall, our study provides promising evidence that disulfiram can be used as a treatment strategy for alcohol-related osteoporosis via the ALDH1A1T–NFATc1 axis.