MicroRNA-186 ameliorates Knee osteoarthritis via regulation of P2X7-mediated Cathepsin-K/Runx2/ADAMTS5 signalling axis in articular chondrocytes.
MicroRNA-186 ameliorates Knee osteoarthritis via regulation of P2X7-mediated Cathepsin-K/Runx2/ADAMTS5 signalling axis in articular chondrocytes.
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MicroRNA-186 通过调节关节软骨细胞中 P2X7 介导的组织蛋白酶-K/Runx2/ADAMTS5 信号轴改善膝骨关节炎
DOI：
10.1016/j.sjbs.2021.06.091
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发表时间：
2021-08
影响因子：
4.4
通讯作者：
Fu X
中科院分区：
文献类型：
--
作者：
Deng R;Zhang H;Huang L;Xiong X;Fu X
膝骨关节炎（KOA）是一种慢性关节疾病，累及关节软骨和滑膜关节周围组织。本研究的主要目的是使用KOA的内侧半月板（DMM）手术去稳定模型确定miR-186- 5 p施用对软骨细胞中致病信号传导表达的影响，并证实KOA大鼠中miR-186对P2 X7介导的RUNX 2/ADAMTS 5轴调节的机制。在关节内注射miR-186- 5 p和阴性对照慢病毒样品八周后，对膝关节软骨组织进行组织病理学分析番红-O/Fast绿色染色。此外，分离关节软骨细胞并使用蛋白质印迹法分析各种蛋白质，包括P2 X7、组织蛋白酶-K、RUNX 2和ADAMTS 5。我们观察到KOA大鼠中P2 X7、组织蛋白酶-K/RUNX 2/ADAMTS 5以及MMP-13的蛋白表达上调，而关节内注射miR-186- 5 p慢病毒可防止这些畸变。因此，该研究得出结论，miR-186协调P2 X7表达和P2 X7介导的组织蛋白酶-K/RUNX 2/ADAMTS 5轴，并调节KOA的发病机制。根据这一证据，我们提出针对miR-186激活的分子治疗干预可能会减轻骨关节炎软骨退化。
Knee osteoarthritis (KOA) is a chronic joint disorder involving the articular cartilage and tissues around the synovial joint. The key objective of this study was to determine the effect of miR-186-5p administration on the expression of pathogenic signalling in the chondrocytes using a surgical destabilization of the medial meniscus (DMM) model of KOA, and to testify the mechanism of P2X7-mediated regulation of RUNX2/ADAMTS5 axis by miR-186 in the KOA rats. After eight weeks of intra-articular injection of the miR-186-5p and negative control lentivirus samples, the knee cartilage tissues were subjected to histopathological analysis Safranin-O/Fast green staining. Further, the articular chondrocytes were separated and analysed for various proteins including P2X7, cathepsin-K, RUNX2 and ADAMTS5 using Western blotting method. We observed that the protein expressions of P2X7, cathepsin-K/RUNX2/ADAMTS5, and also MMP-13 were upmodulated in the KOA rats, while intra-articular miR-186-5p lentivirus administration prevented these aberrations. Hence, the study concludes that miR-186 orchestrates P2X7 expression and the P2X7-mediated cathepsin-K/RUNX2/ADAMTS5 axis and regulates the pathogenesis of KOA. In light of this evidence, we propose that molecular therapeutic interventions targeting miR-186 activation might attenuate osteoarthritic cartilage degeneration.
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