Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China.
Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian, China; Academy of Integrative Medicine, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian 116044, China.
Int Immunopharmacol. 2023 Jul;120:110319. doi: 10.1016/j.intimp.2023.110319. Epub 2023 May 20.
Osteoporosis (OP) is a systemic bone disease caused by an imbalance in osteogenesis and osteoclastic resorption. Extracellular vesicles (EVs)-encapsulated miRNAs from bone mesenchymal stem cells (BMSCs) have been reported to participate in osteogenesis. MiR-16-5p is one of the miRNAs that regulates osteogenic differentiation; however, studies have shown that its role in osteogenesis is controversial. Thus, this study aims to investigate the role of miR-16-5p from BMSC-derived extracellular vesicles (EVs) in osteogenic differentiation and uncover the underlying mechanisms. In this study, we used an ovariectomized (OVX) mouse model and an HO-treated BMSCs model to investigate the effects of BMSC-derived EVs and EV-encapsulated miR-16-5p on OP and the underlying mechanisms. Our results proved that the miR-16-5p level was significantly decreased in HO-treated BMSCs, bone tissues of OVX mice, and lumbar lamina tissues from osteoporotic women. EVs-encapsulated miR-16-5p from BMSCs could promote osteogenic differentiation. Moreover, the miR-16-5p mimics promoted osteogenic differentiation of HO-treated BMSCs, and the effects exerted by miR-16-5p were mediated by targeting Axin2, a scaffolding protein of GSK3β that negatively regulates the Wnt/β-catenin signaling pathway. This study provides evidence that EVs-encapsulated miR-16-5p from BMSCs could promote osteogenic differentiation by repressing Axin2.
骨质疏松症（OP）是一种由成骨和破骨吸收失衡引起的系统性骨病。有研究报道，骨间充质干细胞（BMSCs）来源的细胞外囊泡（EVs）所包裹的 miRNAs 参与成骨作用。miR-16-5p 是调节成骨分化的 miRNAs 之一，然而，研究表明其在成骨中的作用存在争议。因此，本研究旨在探讨 BMSC 来源的细胞外囊泡（EVs）中 miR-16-5p 在成骨分化中的作用，并揭示其潜在机制。在本研究中，我们使用去卵巢（OVX）小鼠模型和 HO 处理的 BMSCs 模型，研究 BMSC 来源的 EVs 和 EV 包裹的 miR-16-5p 对 OP 的影响及其潜在机制。我们的结果证明，HO 处理的 BMSCs、OVX 小鼠的骨组织和骨质疏松症女性的腰椎板组织中 miR-16-5p 的水平显著降低。BMSCs 来源的 EVs 包裹的 miR-16-5p 可促进成骨分化。此外，miR-16-5p 模拟物促进 HO 处理的 BMSCs 的成骨分化，miR-16-5p 的作用是通过靶向 Axin2 介导的，Axin2 是 GSK3β 的支架蛋白，负调控 Wnt/β-catenin 信号通路。本研究提供的证据表明，BMSCs 来源的 EVs 包裹的 miR-16-5p 通过抑制 Axin2 促进成骨分化。
