Xiang Yaoyv, Li Yanlin, Yang Lingjian, He Yinghong, Jia Di, Hu Xidan
Department of Sports Medicine, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, China.
Department of Pharmacy, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, China.
Biochem Res Int. 2020 Jan 24;2020:4508108. doi: 10.1155/2020/4508108. eCollection 2020.
Osteoarthritis (OA) is a chronic joint function disorder with characteristics of chondrocytes reduction and extracellular matrix (ECM) components destruction. MicroRNAs (miRNAs) and the SDF-1/CXCR4 axis are essential factors of chondrocyte apoptosis and ECM degeneration. However, very few studies have investigated the correlation between miRNAs and the SDF-1/CXCR4 axis in osteoarthritis so far. Here, through miRNAs microarray and bioinformatics analyses, we identified miR-142-5p as a CXCR4-targeted and dramatically downregulated miRNA in cartilage from OA patients, as well as in SDF-1-induced OA chondrocytes . In SDF-1-treated primary human OA chondrocytes that were transfected with a miR-142-5p mimic or inhibitor, the expression of CXCR4 was found to be inversely correlated with the expression of miR-142-5p. The dual luciferase reporter assay further verified the target relationship between miR-142-5p and CXCR4. Overexpression of miR-142-5p alleviated OA pathology by suppressing chondrocyte apoptosis, even in CXCR4 overexpressed OA chondrocytes. This was associated with decreased cartilage matrix degradation, reduced cartilage inflammation, and inactivated MAPK signaling pathway. Our study suggests that upregulated expression of CXCR4-targeted miR-142-5p can inhibit apoptosis, inflammation, and matrix catabolism and inactivate the MAPK signaling pathway in OA chondrocytes. Our work provides important insight into targeting miR-142-5p and the SDF-1/CXCR4 axis in OA therapy.
骨关节炎（OA）是一种慢性关节功能障碍，其特征为软骨细胞减少和细胞外基质（ECM）成分破坏。微小RNA（miRNA）和SDF-1/CXCR4轴是软骨细胞凋亡和ECM退变的关键因素。然而，迄今为止，很少有研究探讨骨关节炎中miRNA与SDF-1/CXCR4轴之间的相关性。在此，通过miRNA芯片和生物信息学分析，我们鉴定出miR-142-5p是一种靶向CXCR4且在OA患者软骨以及SDF-1诱导的OA软骨细胞中显著下调的miRNA。在转染了miR-142-5p模拟物或抑制剂的SDF-1处理的原代人OA软骨细胞中，发现CXCR4的表达与miR-142-5p的表达呈负相关。双荧光素酶报告基因检测进一步验证了miR-142-5p与CXCR4之间的靶向关系。miR-142-5p的过表达通过抑制软骨细胞凋亡减轻了OA病理，即使在CXCR4过表达的OA软骨细胞中也是如此。这与软骨基质降解减少、软骨炎症减轻以及MAPK信号通路失活有关。我们的研究表明，靶向CXCR4的miR-142-5p表达上调可抑制OA软骨细胞的凋亡、炎症和基质分解代谢，并使MAPK信号通路失活。我们的工作为在OA治疗中靶向miR-142-5p和SDF-1/CXCR4轴提供了重要的见解。
