Role of HSP90α in osteoclast formation and osteoporosis development

Ma,Jianli; Yang,Chen; Zhong,Huajian; Wang,Cheng; Zhang,Ke; Li,Xiaoming; Wu,Jinhui; Gao,Yang

doi:10.3892/etm.2022.11199

Role of HSP90α in osteoclast formation and osteoporosis development

Authors:
- Jianli Ma
- Chen Yang
- Huajian Zhong
- Cheng Wang
- Ke Zhang
- Xiaoming Li
- Jinhui Wu
- Yang Gao
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Affiliations: Department of Pharmacy, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100039, P.R. China, Department of Orthopedics, Changzheng Hospital, Shanghai 200003, P.R. China, Department of Orthopedics, National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100039, P.R. China, Department of Orthopedics, Shanghai Hospital, Shanghai 200433, P.R. China
Published online on: February 10, 2022 https://doi.org/10.3892/etm.2022.11199
Article Number: 273
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Osteoporosis (OP) is a systemic metabolic bone disease that occurs most frequently in the elderly. The main pathogenesis of OP is excessive proliferation and differentiation of osteoclasts, in which the peroxisome proliferator‑activated receptor γ (PPARγ) pathway has a pivotal role. Recently, heat shock protein (HSP)90α has been identified as an important molecular chaperone with PPARγ, which regulates the effect of the PPARγ pathway. The aim of the present study was to investigate the role of HSP90α involved in the regulation of osteoclast formation and the process of osteoporosis. Firstly, the expression of HSP90α in osteoclast differentiation was detected by western blotting in vitro, then the effect of HSP90α inhibition on the formation and differentiation of osteoclasts was examined. Furthermore, the nuclear import of PPARγ was also assessed to confirm the synergistic effect of HSP90α. Finally, the inhibitory effect of HSP90α in vivo was explored, using a mouse model of osteoporosis. As a result, in the process of osteoclast differentiation and proliferation, the expression of HSP90α was upregulated. Inhibition of HSP90α could block the formation and differentiation of osteoclasts, and remit osteoporosis in mice. Regarding the underlying mechanism, inhibition of HSP90α could block the nuclear import of PPARγ to inhibit osteoclast differentiation and proliferation. In conclusion, these data indicated that the inhibition of HSP90α could block osteoclast formation and remit osteoporosis by reducing the nuclear import of PPARγ.

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