TRIM59 attenuates IL-1β-driven cartilage matrix degradation in osteoarthritis via direct suppression of NF-κB and JAK2/STAT3 signaling pathway.

The tripartite motif (TRIM) protein family are implicated in a wide array of cellular processes, including cell growth, differentiation, apoptosis and inflammation. This study aimed to investigate the specific function of TRIM59 in chondrocytes and its association with the pathophysiology of osteoarthritis (OA). We observed the downregulated TRIM59 expression in OA cartilage compared to normal tissues. Overexpression of TRIM59 suppressed interleukin 1 beta (IL-1β)-induced extracellular matrix (ECM) metabolic imbalance, proinflammatory cytokine production, apoptosis and decrease in cell viability. Mechanistic analyses further revealed that IL-1β-induced activation of the NF-κB and JAK2/STAT3 pathway is suppressed upon TRIM59 overexpression. TRIM59 expression was consistently decreased in a rat OA model in vivo , and its overexpression led to inhibition of matrix metallopeptidase-13 (MMP-13) production, proinflammatory cytokine levels and increased collagen type II (collagen II) and aggrecan synthesis. Our data collectively suggest that TRIM59 plays a critical in OA development through regulation of NF-κB and JAK2/STAT3 signaling pathway. Pharmacological upregulation of TRIM59 may therefore present an effective novel therapeutic approach for OA. • TRIM59 expression is downregulated in human OA cartilage and IL-1β-induced chondrocytes. • TRIM59 attenuates IL-1β-induced chondrocyte apoptosis, inflammatory response and matrix degradation. • TRIM59 counteracted cartilage matrix degradation in the rat OA model. • TRIM59 represses IL-1β activated NF-κB and JAK2/STAT3 signaling pathway activation in chondrocytes. [ABSTRACT FROM AUTHOR]