miR-122/SIRT1 axis regulates chondrocyte extracellular matrix degradation in osteoarthritis

Abstract

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. Methods: 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. Results: 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. Conclusion: The miR-122/SIRT1 axis can regulate the degradation of ECM in OA, thus providing new insights into the treatment of OA.

Regulation of inflammatory and catabolic responses to IL-1β in rat articular chondrocytes by microRNAs miR-122 and miR-451

“…MicroRNA technology is a developing field; thus, there is variability in reported results, due in part to differences in cell models or tissue source. In contrast to our observation that miR-122 caused a marked decrease in MMP-13 in rArCs, a recent paper by Bai and colleagues reported that miR-122 increased MMP-13 expression and protein levels in SW1353 cells 35 . Both studies observed decreased expression of collagen II and aggrecan mRNAs.…”

Roflumilast Reduced the IL-18-Induced Inflammatory Response in Fibroblast-Like Synoviocytes (FLS)

“…It has been demonstrated that ECM can be degraded by metalloproteinases such as MMP-3 and MMP-9 in osteoarthritis. 27 Similarly, in our study, we found that treatment with roflumilast significantly reduced the production of MMP-3 and MMP-9 in IL-18-induced FLS. This finding indicates that roflumilast might have a potential effect in preventing the degradation of cartilage.…”

Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA–SIRT2 Axis and Its Relationship with Aging-Related Diseases

“…As mentioned above, miR-122 targets SIRT1, and this axis is reported to regulate chondrocyte extracellular matrix degradation in the cartilage of osteoarthritis [ 56 ]. The expression of miR-122 was increased in osteoarthritis cartilage compared to healthy controls, while SIRT1 expression was decreased.…”

“…The expression of miR-122 was increased in osteoarthritis cartilage compared to healthy controls, while SIRT1 expression was decreased. The overexpression of miR-122 increased extracellular matrix catabolic factors, such as disintegrins and matrix metalloproteinases, and inhibited the expression of synthetic metabolic genes, such as collagen II and aggregating proteoglycan, partly via SIRT1 [ 56 ]. In the liver, miR-122 and SIRT6 negatively regulate each other’s expression, and they oppositely regulate a similar set of metabolic genes and fatty acid β-oxidation [ 57 ].…”