IL‐1β‐induced miR‐34a up‐regulation inhibits Cyr61 to modulate osteoarthritis chondrocyte proliferation through ADAMTS‐4

다국어 초록 (Multilingual Abstract)

Osteoarthritis (OA) is the most prevalent degenerative joint disease with multifactorial etiology caused by risk factors. The degradation of aggrecan by upregulated ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is the key event in the development of OA. ADAMTS‐4 contributes to aggrecan degradation in human OA. Cysteine‐rich angiogenic inducer 61 (Cyr61), which is associated with diseases related to chronic inflammation, is found in articular cartilage from patients with osteoarthritis and appears to suppress ADAMTS‐4 activity, possibly leading to chondrocyte cloning. Herein, we first revealed that Cyr61 and ADAMTS‐4 protein levels were remarkably increased in OA cartilage tissues and OA chondrocytes, and verified Cyr61 regulation of ADAMTS‐4 in normal and OA chondrocyte. Further, we revealed that Cyr61 could promote OA chondrocyte proliferation through inhibiting ADAMTS‐4. Overproduction of inflammatory cytokines plays a vital role in the pathological development of OA; herein, we demonstrated that IL‐1β inhibited Cyr61, while promoted ADAMTS‐4 expression. By using online tools and luciferase assays, we confirmed that miR‐34a, a regulatory miRNA of chondrocyte proliferation, could directly bind to the 3′‐UTR of Cyr61 to inhibit its expression; further, IL‐1β regulated Cyr61 and ADAMTS‐4 expression through miR‐34a. In OA cartilage tissues, miR‐34a, and IL‐1β mRNA expression was up‐regulated and positively correlated; miR‐34a and Cyr61 mRNA was positively correlated, further indicating that suppressing miR‐34a expression might rescue IL‐1β‐induced Cyr61 suppression, and promote OA chondrocyte proliferation. Taken together, we provided novel experimental basis for rescuing OA chondrocyte proliferation through miR‐34a/Cyr61 axis.
IL‐1β‐induced miR‐34a up‐regulation inhibits Cyr61 to modulate osteoarthritis chondrocyte proliferation, which provided novel experimental basis for rescuing OA chondrocyte proliferation through miR‐34a/Cyr61 axis.