Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties.
Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties.
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褪黑激素通过保留 SIRT1 介导的细胞内抗氧化特性来恢复骨髓间充质干细胞因骨质疏松而受损的成骨潜力。
DOI：
10.1016/j.freeradbiomed.2019.10.412
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发表时间：
2020-01
影响因子：
7.4
通讯作者：
He, Fan
中科院分区：
文献类型：
--
作者：
Chen, Weikai;Chen, Xi;Chen, Angela Carley;Shi, Qin;Pan, Guoqing;Pei, Ming;Yang, Huilin;Liu, Tao;He, Fan
绝经后骨质疏松症（OP）是影响数百万老年妇女的最常见的骨骼疾病之一。骨质疏松患者骨髓间充质干细胞（BMMSCs）的成骨减少和氧化应激增加。褪黑激素对成骨细胞分化和骨形成具有积极作用;然而，褪黑激素是否可以恢复OP受损的BMMSCs的成骨潜能以及其潜在机制尚不清楚。本研究的目的是研究（1）褪黑激素是否可以通过保护OP BMMSCs的抗氧化功能来恢复其受损的成骨潜能，以及（2）静脉注射褪黑激素是否可以预防OP诱导的去卵巢大鼠骨丢失。切除雌性大鼠卵巢，3个月后分离大鼠骨髓间充质干细胞。在体外治疗与褪黑激素成功地提高了成骨分化的OP BMMSCs，证明了增加的基质矿化和成骨细胞特异性基因的水平。在褪黑激素处理的OP BMMSCs中，细胞内氧化应激显著减弱，而细胞内抗氧化酶的水平显著上调-特别是超氧化物歧化酶2（SOD 2）和谷胱甘肽过氧化物酶1（GPX 1）。沉默信息调节因子1（SIRT 1）参与褪黑激素介导的骨生成和抗氧化功能的恢复。同时，通过尾静脉注射褪黑激素成功地改善了去卵巢大鼠股骨的骨微结构。进一步的实验证实，从褪黑激素处理的OVX大鼠来源的BMMSCs表现出良好的保存抗氧化特性和成骨潜力。我们的研究结果表明，褪黑激素的管理是一个很有前途的策略，治疗绝经后OP患者的抗氧化性能和成骨潜能的BMMSCs。
Postmenopausal osteoporosis (OP) is one of the most common bone diseases that affects millions of aging women. Reduced osteogenesis and increased oxidative stress have been implicated in bone marrow mesenchymal stem cells (BMMSCs) derived from OP patients. Melatonin has shown positive effects on osteoblast differentiation and bone formation; however, it was unknown whether melatonin could restore OP-impaired osteogenic potential of BMMSCs and what the underlying mechanisms entailed. The objective of this study is to investigate (1) whether melatonin can restore the impaired osteogenic potential of OP BMMSCs by preserving their antioxidant functions, and if so, (2) whether intravenous administration of melatonin can prevent OP-induced bone loss in ovariectomized (OVX) rats. Ovariectomies were performed in female rats and BMMSCs were isolated from the osteoporotic rats 3 months later. In vitro treatment with melatonin successfully improved the osteogenic differentiation of OP BMMSCs, as evidenced by increased levels of matrix mineralization and osteoblast-specific genes. In melatonin-treated OP BMMSCs, intracellular oxidative stress was significantly attenuated, while levels of intracellular antioxidant enzymes were noticeably up-regulated – particularly superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1). Silent information regulator type 1 (SIRT1) was involved in the melatonin-mediated recovery of osteogenesis and antioxidant functions. Meanwhile, in vivo injections of melatonin via the tail vein successfully ameliorated the bone micro-architecture in ovariectomized rat femurs. Further experiments confirmed that BMMSCs derived from melatonin-treated OVX rats exerted well-preserved antioxidant properties and osteogenic potential. Our findings demonstrate that the administration of melatonin is a promising strategy for treating patients with postmenopausal OP by preserving the antioxidant properties and osteogenic potential of their BMMSCs.
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DOI：
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发表时间：
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期刊：
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影响因子：
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