The validity of CCN3 in knee osteoarthritis: clinical and musculoskeletal ultrasound evaluation

Abstract Background Knee osteoarthritis (KOA) is a prevalent degenerative joint condition marked by progressive loss of articular cartilage and chronic inflammation. Recent studies have recognized Cellular Communication Network Factor 3 (CCN3) as a potential regulator of cartilage homeostasis and inflammation. However, its role in OA pathogenesis and flare-ups remains under investigations. Aim to assess serum CCN3 levels in primary KOA and to evaluate its correlation with OA activity, severity, and musculoskeletal ultrasound (MSUS) findings. Methodology This case-control research involved 100 participants: fifty primary KOA patients and fifty age-and sex-matched healthy controls. All participants underwent clinical assessment, evaluation of OA activity by KOA flare up score (KOFUS) and severity by Lequesne index, laboratory investigations including CBC, CRP, ESR, and serum CCN3, radiographic evaluation by Xray using Kellgren-Lawrence score and by MSUS using the Outcome Measures in Rheumatology (OMERACT) ultrasound scores for KOA. Results Serum CCN3 levels were significantly increased in OA cases in comparison with controls (P<0.001). ROC analysis demonstrated good predictive value for OA (AUC=0.743) with 84% sensitivity and 64% specificity at a cut-off of 2209.9 pg/ml. Although no significant correlations were found between CCN3 and Lequesne, KOFUS, Kellgren-Lawrence, or OMERACT scores, patients experiencing flare-ups showed significantly higher CCN3 levels, OMERACT and Lequesne scores than those without flares (P=0.037,0.001,0.001 respectively). Conclusions Serum CCN3 is significantly elevated in patients with primary KOA, particularly during flare-ups, indicating its potential role as a biomarker of inflammatory activity. However, its lack of correlation with structural damage scores suggests a limited role in reflecting disease severity.