Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
Bone. 2024 Nov;188:117224. doi: 10.1016/j.bone.2024.117224. Epub 2024 Aug 6.
Postmenopausal osteoporosis (PMOP) is a metabolic disorder characterized by the loss of bone density, which increases the risk of developing complications such as fractures. A pivotal factor contributing to the onset of PMOP is the diminished osteogenic differentiation capacity of bone marrow mesenchymal stem cells (BMSCs). MicroRNAs (miRNAs) play a substantial role in this process; however, their specific impact on regulating BMSCs osteogenesis remains unclear. Studies have evidenced a reduced expression of miR-18a-5p in PMOP, and concomitantly, our observations indicate an augmented expression of miR-18a-5p during the osteogenic differentiation of BMSCs. This investigation seeks to elucidate the regulatory influence of miR-18a-5p on BMSC osteogenic differentiation and the underlying mechanisms. In vitro experiments demonstrated that the overexpression of miR-18a-5p facilitated the osteogenic differentiation of BMSCs, while the downregulation of miR-18a-5p yielded converse outcomes. Mechanistically, We employed bioinformatics techniques to screen out the target gene Notch2 of miR-18a-5p. Subsequently, dual-luciferase reporter gene assays and rescue experiments substantiated that miR-18a-5p promotes BMSC osteogenic differentiation by suppressing Notch2. Finally, miR-18a-5p was overexpressed via adenovirus injection into the femoral bone marrow cavity, with results demonstrating its capability to enhance osteogenic differentiation and alleviate PMOP symptoms. Our findings disclose that miR-18a-5p fosters osteogenic differentiation of BMSC by inhibiting Notch2, thereby offering novel targets and strategies for PMOP treatment.
绝经后骨质疏松症（PMOP）是一种以骨密度丧失为特征的代谢紊乱疾病，增加了发生骨折等并发症的风险。导致 PMOP 发生的一个关键因素是骨髓间充质干细胞（BMSCs）的成骨分化能力下降。微小 RNA（miRNAs）在这个过程中起着重要作用；然而，它们对调节 BMSCs 成骨作用的确切影响尚不清楚。研究表明，miR-18a-5p 在 PMOP 中表达降低，同时，我们的观察表明，miR-18a-5p 在 BMSCs 成骨分化过程中表达增加。本研究旨在阐明 miR-18a-5p 对 BMSC 成骨分化的调节作用及其机制。体外实验表明，miR-18a-5p 的过表达促进了 BMSCs 的成骨分化，而 miR-18a-5p 的下调则产生了相反的结果。机制上，我们采用生物信息学技术筛选出 miR-18a-5p 的靶基因 Notch2。随后，双荧光素酶报告基因检测和挽救实验证实，miR-18a-5p 通过抑制 Notch2 促进 BMSC 成骨分化。最后，通过腺病毒注射到股骨骨髓腔中转染 miR-18a-5p 以实现过表达，结果表明其具有增强成骨分化和缓解 PMOP 症状的能力。我们的研究结果揭示，miR-18a-5p 通过抑制 Notch2 促进 BMSC 的成骨分化，为 PMOP 的治疗提供了新的靶点和策略。
