MicroRNA-92b-5p modulates melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells by targeting ICAM-1

MicroRNA-92b-5p 通过靶向 ICAM-1 调节褪黑素介导的骨髓间充质干细胞成骨分化

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作者:Yuan Li, Chao Feng, Manqi Gao, Mengyu Jin, Tianyi Liu, Ye Yuan, Gege Yan, Rui Gong, Yi Sun, Mingyu He, Yutuo Fu, Lai Zhang, Qi Huang, Fengzhi Ding, Wenya Ma, Zhenggang Bi, Chaoqian Xu, Natalia Sukhareva, Djibril Bamba, Russel Reiters, Fan Yang, Benzhi Cai, Lei Yang

Abstract

Osteoporosis is closely associated with the dysfunction of bone metabolism, which is caused by the imbalance between new bone formation and bone resorption. Osteogenic differentiation plays a vital role in maintaining the balance of bone microenvironment. The present study investigated whether melatonin participated in the osteogenic commitment of bone marrow mesenchymal stem cells (BMSCs) and further explored its underlying mechanisms. Our data showed that melatonin exhibited the capacity of regulating osteogenic differentiation of BMSCs, which was blocked by its membrane receptor inhibitor luzindole. Further study demonstrated that the expression of miR-92b-5p was up-regulated in BMSCs after administration of melatonin, and transfection of miR-92b-5p accelerated osteogenesis of BMSCs. In contrast, silence of miR-92b-5p inhibited the osteogenesis of BMSCs. The increase in osteoblast differentiation of BMSCs caused by melatonin was attenuated by miR-92b-5p AMO as well. Luciferase reporter assay, real-time qPCR analysis and western blot analysis confirmed that miR-92b-5p was involved in osteogenesis by directly targeting intracellular adhesion molecule-1 (ICAM-1). Melatonin improved the expression of miR-92b-5p, which could regulate the differentiation of BMSCs into osteoblasts by targeting ICAM-1. This study provided novel methods for treating osteoporosis.

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