High C1r expression is associated with cartilage damage in post-traumatic osteoarthritis

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The complement system undergoes extensive activation in osteoarthritis. Nevertheless, the specific function of C1r, a constituent of this system, in post-traumatic osteoarthritis (PTOA) remains unclear.

To explore the clinical value and function of C1r in PTOA.

Synovial fluid was obtained from 90 patients diagnosed with PTOA and 86 patients with knee joint injuries. Three specimens were randomly selected from each group for proteomic examination. The expression of C1r in all these specimens was determined via RT-qPCR, followed by ROC curve analysis and logistic regression analysis. The expression of C1r, apoptosis, and cytokine levels in chondrocytes and mouse cartilage tissues were detected through Western blotting/immunohistochemistry, flow cytometry/TUNEL, and ELISA.

Proteomic analysis unveiled 51 proteins that exhibited down-regulation in PTOA and identified 309 up- regulated proteins, among which C1r was included. RT-qPCR analysis of all samples indicated that C1R was significantly up-regulated in the PTOA cohort and demonstrated a moderate discriminatory ability between PTOA patients and non-PTOA individuals (AUC = 0.777). After adjustment for other confounding factors, C1R was determined to be potentially related to PTOA occurrence. High expression of C1R was correlated with a higher Kellgren-Lawrence grade and a lower Knee Injury and Osteoarthritis Outcome Score. C1r was overexpressed in PTOA cells and mouse cartilage tissues, and its silencing led to a reduction in apoptosis, as well as the levels of inflammatory factors (IL-6/IL-8) and matrix catabolic enzymes (MMP-13/ADAMTS-4) in chondrocytes and cartilage tissues.

C1r serves as a potential candidate biomarker for PTOA and warrants further in-depth exploration. In experimental models, targeting C1r may contribute to the mitigation of cartilage damage.