Melatonin alleviates hydrogen peroxide induced oxidative damage in MC3T3-E1 cells and promotes osteogenesis by activating SIRT1

Abstract

Oxidative stress is an important contributor to the development of osteoporosis. Melatonin, an indoleamine secreted by the pineal gland, has antioxidant properties. This study aims to explore whether melatonin can promote bone formation and elucidate the mechanisms underlying this process. In this study, we used an in vitro hydrogen peroxide (H₂O₂)-induced oxidative stress model in MC3T3-E1 cells and an in vivo ovariectomized osteoporotic bone defect model in rats to explore the protective effects of melatonin against osteoporotic bone defects along with the mechanism underlying these effects. We found that melatonin significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of BMP2, RUNX2, and OPN in MC3T3-E1 cells treated with H₂O₂. Furthermore, melatonin was found to activate SIRT1, SIRT3 and inhibit p66Shc, reduce the intracellular reactive oxygen species levels, stabilize mitochondria, reduce malondialdehyde levels, increase superoxide dismutase activity, and reduce apoptosis in MC3T3-E1 cells treated with H₂O₂. Intriguingly, these effects could be reversed by the SIRT1 inhibitor EX527. In vivo experiments confirmed that melatonin improves the microstructure and bone mineral density of the distal femoral bone trabecula and promotes bone formation. Meanwhile, melatonin activated SIRT1, inhibited p66Shc and increased SIRT3 expression. Taken together, our findings showed that melatonin can restrain oxidative damage in MC3T3-E1 cells and promote osteogenesis by activating SIRT1 which regulate the activity of SIRT3 and inhibit the expression of p66Shc, suggesting that melatonin could be a potential therapeutic agent for osteoporosis-related bone metabolic diseases.

Keywords:

• Melatonin
• osteogenesis
• osteoporosis
• osteoporotic bone defect
• ROS
• SIRT1/p66Shc/SIRT3 pathway

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by the National Natural Science Foundation of China [81341054, 81171732], Talented Scholars of Wannan Medical College [YR201917], Technology Mountaineering Program of Yijishan Hospital, and Wannan Medical College [PF2019005].