miR-18a-5p promotes osteogenic differentiation of BMSC by inhibiting Notch2

IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Bone Pub Date : 2024-08-06 DOI:10.1016/j.bone.2024.117224
Peipei He , Zefeng Yang , Hetong Li , Enhui Zhou , Zuoxu Hou , Hongxun Sang
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Abstract

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.

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miR-18a-5p 通过抑制 Notch2 促进 BMSC 的成骨分化。
绝经后骨质疏松症(PMOP)是一种以骨密度丧失为特征的代谢性疾病,会增加发生骨折等并发症的风险。导致绝经后骨质疏松症发病的一个关键因素是骨髓间充质干细胞(BMSCs)的成骨分化能力减弱。微小核糖核酸(miRNA)在这一过程中发挥着重要作用;然而,它们对调节骨髓间充质干细胞成骨的具体影响仍不清楚。研究表明,在 PMOP 中,miR-18a-5p 的表达量减少,与此同时,我们的观察表明,在 BMSCs 成骨分化过程中,miR-18a-5p 的表达量增加。本研究旨在阐明 miR-18a-5p 对 BMSC 成骨分化的调控作用及其内在机制。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 的下调则产生相反的结果。从机理上讲,我们利用生物信息学技术筛选出了 miR-18a-5p 的靶基因 Notch2。随后,双荧光素酶报告基因实验和拯救实验证实,miR-18a-5p 通过抑制 Notch2 促进 BMSC 成骨分化。最后,miR-18a-5p通过腺病毒注射到股骨髓腔中进行过表达,结果表明它能促进成骨分化并缓解PMOP症状。我们的研究结果表明,miR-18a-5p 可通过抑制 Notch2 促进骨髓造血干细胞的成骨分化,从而为治疗 PMOP 提供了新的靶点和策略。
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来源期刊
Bone
Bone 医学-内分泌学与代谢
CiteScore
8.90
自引率
4.90%
发文量
264
审稿时长
30 days
期刊介绍: BONE is an interdisciplinary forum for the rapid publication of original articles and reviews on basic, translational, and clinical aspects of bone and mineral metabolism. The Journal also encourages submissions related to interactions of bone with other organ systems, including cartilage, endocrine, muscle, fat, neural, vascular, gastrointestinal, hematopoietic, and immune systems. Particular attention is placed on the application of experimental studies to clinical practice.
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