Effects of IL-1β-induced ADAMTS-4/-5 and TAK1 on the degradation of cartilage aggrecan in the progression of human osteoarthritis

Abstract

Objective Interleukin-1β (IL-1β) is a potentially important cytokine involved in several pathological processes of osteoarthritis (OA). It is well known that a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4/-5) and transforming growth factor-β activated kinase 1 (TAK1) contribute to the degradation of human OA cartilage aggrecan. The purpose of this study was to investigate the mechanism by which IL-1β induced the expression of ADAMTS-4/-5 and TAK1 in human OA cartilage aggrecan degradation. Methods The pathological changes of cartilage tissues and chondrocytes were observed by histomorphological analysis. OA chondrocytes were isolated from human articular cartilage tissues and stimulated with 10 ng/ml of IL-1β at the per-designed times (24 h, 48 h, 72 h). Expression of ADAMTS-4/-5 and TAK1 in cartilage tissues and chondrocytes were measured using immunohistochemistry (IHC) and Western blot (WB). Results The level of IL-1β in synovial fluid in the normal group was significantly lower than that in OA group. The expression of ADAMTS-4/-5 and TAK1 were simultaneously upregulated in human OA cartilage tissues,and ADAMTS-4 was more positively correlated with TAK1 than ADAMTS-5. Furthermore, the expression of ADAMTS-4/-5 and TAK1 were increased by stimulation with IL-1β in human OA chondrocytes, but no positive correlation was found. Conclusion It is proposed that reducing the expression of ADAMTS-4/-5 in prevention of OA may involve the inhibition of TAK1 activity.