Department of Orthopedics, Huizhou Third People's Hospital, Guangzhou Medical University, Huizhou City 516002, Guangdong Province, P.R. China.
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20191908.
BACKGROUND/AIMS: MicroRNAs (miRNAs) are involved in the pathogenesis of osteoarthritis (OA). The present study aimed to investigate the potential function of miR-122 in the development of OA and its potential molecular mechanisms.
The expression of miR-122, silent information regulator 1 (SIRT1), collagen II, aggrecan, matrix metalloproteinase (MMP) 13 (MMP13) and ADAMTS4 in OA cartilage was detected by RT-qPCR. Target gene prediction and screening, luciferase reporter assay were used to verify downstream target genes of miR-122.
Compared with osteonecrosis, the expression of miR-122 was significantly increased in OA cartilage, while the expression of SIRT1 was significantly decreased. Overexpression of miR-122 increased the expression of extracellular matrix (ECM) catabolic factors, for example disintegrins, MMPs and metalloproteinases with platelet reaction protein motifs, and inhibited the expression of synthetic metabolic genes such as collagen II and aggregating proteoglycan. Inhibition of miR-122 expression had the opposite effect. Furthermore, SIRT1 was identified as a direct target of miR-122. SIRT1 was significantly inhibited by miR-122 overexpression. Knockdown of SIRT1 reversed the degradation of chondrocyte ECM by miR-122 inhibitors.
The miR-122/SIRT1 axis can regulate the degradation of ECM in OA, thus providing new insights into the treatment of OA.
背景/目的：微小 RNA（miRNA）参与骨关节炎（OA）的发病机制。本研究旨在探讨 miR-122 在 OA 发展中的潜在作用及其潜在的分子机制。
采用 RT-qPCR 检测 OA 软骨中 miR-122、沉默信息调节因子 1（SIRT1）、II 型胶原、聚集蛋白聚糖、基质金属蛋白酶（MMP）13（MMP13）和 ADAMTS4 的表达。采用靶基因预测和筛选、荧光素酶报告基因检测实验验证 miR-122 的下游靶基因。
与骨坏死相比，miR-122 在 OA 软骨中的表达显著增加，而 SIRT1 的表达显著降低。miR-122 的过表达增加了细胞外基质（ECM）降解因子的表达，例如分解素、MMPs 和具有血小板反应蛋白基序的金属蛋白酶，抑制了胶原 II 和聚集蛋白聚糖等合成代谢基因的表达。抑制 miR-122 的表达则产生相反的效果。此外，SIRT1 被鉴定为 miR-122 的直接靶基因。miR-122 过表达显著抑制 SIRT1。SIRT1 的敲低逆转了 miR-122 抑制剂对软骨细胞 ECM 的降解作用。
miR-122/SIRT1 轴可调节 OA 中 ECM 的降解，从而为 OA 的治疗提供新的见解。
