Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 176, Issue -, Pages 228-240Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2021.07.016
Keywords
Osteonecrosis; SIRT3; Oxidative stress; Resveratrol
Funding
- National Natural Science Foundation of China [:81772348]
- National Key Research and Development Project of China [2017YFB1304200]
- Wenzhou Science and Technology Bureau [Y20180028]
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The study indicates the important role of SIRT3 in glucocorticoid-induced osteonecrosis of the femoral head. Resveratrol can reduce oxidative stress and mitochondrial damage by activating SIRT3, and promote osteogenic differentiation of BMSCs through the AMPK/PGC-1 alpha/SIRT3 axis. Resveratrol administration can prevent GIONFH, enhance SIRT3 expression, and reduce oxidative levels in affected rats.
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-1 alpha/ 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.
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