International Journal of Medical Sciences

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21 November 2018

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Int J Med Sci 2018; 15(10):1083-1091. doi:10.7150/ijms.26314

Research Paper

Melatonin alleviates oxidative stress-inhibited osteogenesis of human bone marrow-derived mesenchymal stem cells through AMPK activation

Sooho Lee1, Nhu Huynh Le1,2, Dongchul Kang1,2✉

1. Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 14066, Republic of Korea.
2. Department of Biomedical Gerontology, Hallym University Graduate School, Chuncheon, Gangwon-do 24252, Republic of Korea.

Abstract

Oxidative stress plays an important role in the pathogenesis of aging-related osteoporosis through the increased bone resorption or reduced bone formation. Melatonin, which can exert beneficial actions through antioxidant, anti-inflammatory, and bone-preserving effects, shows promise in preventing oxidative stress-inhibited osteogenesis. However, specific mechanisms by which melatonin rescues oxidative stress-inhibited osteogenesis of human mesenchymal stem cells (MSCs) have not been fully elucidated yet. We therefore investigated whether activation of AMPK by melatonin regulates the antagonistic crosstalk between oxidative stress and osteogenic differentiation in human MSCs. Melatonin treatment significantly enhanced osteogenic differentiation of human MSCs through activation of AMPK and upregulation of FOXO3a and RUNX2 which were known as master transcription factors responsible for the mechanistic link between oxidative stress and osteogenic phenotype. Osteogenic differentiation determined by calcium deposition was significantly increased by melatonin treatment against oxidative stress. In addition, melatonin treatment reconstituted activation of AMPK and expression of FOXO3a and RUNX2 inhibited by oxidative stress. Overall, these results demonstrate that melatonin enhances osteogenic differentiation of human MSCs and restores oxidative stress-inhibited osteogenesis through AMPK activation in human MSCs, suggesting that activation of AMPK by melatonin may represent a promising new therapeutic strategy for treating metabolic bone diseases such as osteoporosis.

Keywords: melatonin, oxidative stress, mesenchymal stem cells, osteogenesis, AMPK, osteoporosis

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How to cite this article:
Lee S, Le NH, Kang D. Melatonin alleviates oxidative stress-inhibited osteogenesis of human bone marrow-derived mesenchymal stem cells through AMPK activation. Int J Med Sci 2018; 15(10):1083-1091. doi:10.7150/ijms.26314. Available from http://www.medsci.org/v15p1083.htm