CD5L is a potential negative regulator of chondrocyte apoptosis in osteoarthritis

Objectives: CD5 antigen-like (CD5L) protein is a scavenger receptor involved in inflammation control and enriched in the synovial fluid and membranes of osteoarthritis (OA) patients. Although increased CD5L levels have been associated with OA pathology, its direct role in chondrocytes and contribution to cartilage degeneration remain unknown. We investigated the impact of CD5L on human chondrocytes in the context of OA. Methods: We compared CD5L mRNA levels in primary chondrocytes between OA patients and unaffected controls. We also measured CD5L levels in two chondrocyte cell lines under conditions mimicking OA. RNAseq was performed to determine the effects of increasing CD5L expression on the chondrocyte transcriptome. Finally, we studied the influence of CD5L levels on chondrocyte survival by depleting or overexpressing CD5L in chondrocyte cell lines. Results: CD5L transcript levels were higher in primary chondrocytes from OA patients than in those from controls. Treatment with the pro-inflammatory cytokine IL1β or doxorubicin further induced CD5L expression in primary and cultured chondrocytes. Transcriptomic analysis revealed a correlation between high CD5L transcript levels and expression of genes involved in programmed cell death, inflammation, and differentiation. CD5L knockout increased survival of doxorubicin-treated chondrocytes and reduced apoptosis marker levels compared to non-targeting controls. Conclusion: . CD5L is therefore a potential target for OA management.