Department of Orthopedic Surgery, The People's Hospital of Yuxi City, The 6th Affiliated Hospital of Kunming Medical University, Yuxi, Yunnan 653100, China.
Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223200, China.
Biomed Res Int. 2018 Mar 29;2018:3274641. doi: 10.1155/2018/3274641. eCollection 2018.
Osteoporosis is a systemic bone metabolic disease that is highly prevalent in the elderly population, particularly in postmenopausal women, which results in enhanced bone fragility and an increased susceptibility to fractures. However, the underlying molecular pathogenesis mechanisms still remain to be further elucidated. In this study, in a rat ovariectomy- (OVX-) induced postmenopausal osteoporosis model, aberrant expression of a microRNA miR-142-5p and vascular cell adhesion molecule 1 (VCAM-1) was found by RNA sequencing analysis and qRT-PCR. Using a dual-luciferase reporter assay, we found that miR-142-5p can bind to and decrease expression of VCAM-1 mRNA. Such reduction was prohibited when the miR-142-5p binding site in VCAM-1 3'UTR was deleted, and Western blotting analyses validated the fact that miR-142-5p inhibited the expression of VCAM-1 protein. Bone marrow-derived mesenchymal stem cells (BMMSCs) transfected with miR-142-5p showed a significantly decreased migration ability in a Transwell migration assay. Collectively, these data indicated the important role of miR-142-5p in osteoporosis development involving targeting VCAM-1 and inhibiting BMMSC migration.
骨质疏松症是一种全身性骨代谢疾病，在老年人群中发病率很高，尤其是绝经后妇女，导致骨脆性增加，骨折易感性增加。然而，其潜在的分子发病机制仍有待进一步阐明。在这项研究中，通过 RNA 测序分析和 qRT-PCR 发现，在大鼠卵巢切除（OVX）诱导的绝经后骨质疏松模型中，微小 RNA miR-142-5p 和血管细胞黏附分子 1（VCAM-1）的表达异常。通过双荧光素酶报告基因检测，我们发现 miR-142-5p 可以结合并降低 VCAM-1 mRNA 的表达。当 VCAM-1 3'UTR 中的 miR-142-5p 结合位点被删除时，这种降低被禁止，Western blot 分析验证了 miR-142-5p 抑制 VCAM-1 蛋白表达的事实。转染 miR-142-5p 的骨髓间充质干细胞（BMMSCs）在 Transwell 迁移实验中表现出明显降低的迁移能力。综上所述，这些数据表明 miR-142-5p 通过靶向 VCAM-1 抑制 BMMSC 迁移在骨质疏松症的发生发展中起重要作用。
