2. Academic Validation
  3. Therapeutic effect of SIRT3 on glucocorticoid-induced osteonecrosis of the femoral head via intracellular oxidative suppression

Therapeutic effect of SIRT3 on glucocorticoid-induced osteonecrosis of the femoral head via intracellular oxidative suppression

  • Free Radic Biol Med. 2021 Nov 20;176:228-240. doi: 10.1016/j.freeradbiomed.2021.07.016.
Liang Chen 1,  Bing-Zhang Wang 1,  Jun Xie 1,  Ri-Yan Zhang 2,  Chen Jin 1,  Wei-Kai Chen 3,  Kang-Hao Fang 1,  Chen-Xuan Hong 1,  Tian-Hao Xu 1,  Cheng-Bin Huang 1,  Lei Yang 4,  She-Ji Weng 5
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang, China.
  • 2 School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, 325000, China.
  • 3 School of Medicine, Shanghai University, Shanghai, 200444, China.
  • 4 Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang, China; School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: cl18958749973@163.com.
  • 5 Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang, China. Electronic address: wsj_wmu@163.com.
PMID: 34260898 DOI: 10.1016/j.freeradbiomed.2021.07.016
Abstract

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a serious complication after long-term or excess administration of clinical glucocorticoids intervention, and the pathogenic mechanisms underlying have not been clarified yet. Oxidative stress is considered as a major cause of bone homeostasis disorder. This study is aimed to explore the potential relevance between SIRT3 and GIONFH, as well as the effect of resveratrol, which has been reported for its role in SIRT3 activation, on dexamethasone-induced oxidative stress and mitochondrial compromise in bone marrow stem cells (BMSCs). In this study, our data showed that SIRT3 level was declined in GIONFH rat femoral head, corresponding to a resultant decrease of SIRT3 expression in dexamethasone-treated BMSCs in vitro. We also found that dexamethasone could result in oxidative injury in BMSCs, and resveratrol treatment reduced this deleterious effect via a SIRT3-dependent manner. Moreover, our results demonstrated that rewarding effect of resveratrol on BMSCs osteogenic differentiation was via activation of AMPK/PGC-1α/SIRT3 axis. Meanwhile, resveratrol administration prevented the occurrence of GIONFH, enhanced SIRT3 expression and reduced oxidative level in GIONFH model rats. Therefore, our study provides basic evidence that SIRT3 may be a promising therapeutic target for GIONFH treatment and resveratrol could be an ideal agent for clinical uses.

Keywords

Osteonecrosis; Oxidative stress; Resveratrol; SIRT3.

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