The IL-1β/AP-1/miR-30a/ADAMTS-5 axis regulates cartilage matrix degradation in human osteoarthritis

The proinflammatory cytokine interleukin-1β (il-1β) is involved in the initiation and progression of osteoarthritis (oa) by stimulating the expression of matrix-degrading proteinases, such as a disintegrin metalloproteinase with thrombospondin motifs-5 (adamts-5), a key player in oa pathogenesis. however, how il-1β induces adamts-5 overexpression is poorly understood. we demonstrate that il-1β regulates adamts-5 expression by suppressing microrna-30a (mir-30a). bioinformatics was performed to predict mirnas targeting adamts-5. mir-30a inhibited adamts-5 expression by directly targeting its 3′-untranslated region. mir-30a expression was downregulated in oa patients and was negatively correlated with adamts-5 expression and positively correlated with hospital for special surgery (hss) scores. il-1β suppressed mir-30a expression by recruiting the activator protein (ap-1) transcription factor c-jun/c-fos to the mir-30a promoter. il-1β-induced c-jun/c-fos expression regulated adamts-5 expression and cartilage matrix degradation via mir-30a in human chondrocytes. these data indicate that the il-1β/ap-1/mir-30a/adamts-5 pathway contributes to il-1β-induced cartilage matrix degradation in human oa chondrocytes. mir-30a act as a pivotal regulator of cartilage homeostasis and a potential diagnostic and therapeutic target for oa.