Knee synovial fluid complement C3- chain levels correlate with clinical symptoms of knee osteoarthritis

Aim Early research found innate immune factor complement C3 in the synovial fluid (SF) and activated in serum of osteoarthritis (OA) patients. Whether synovial C3 comes from circulation, or is produced locally, is still unknown. It is also unclear whether synovial and circulating C3 is responsible to OA symptoms. A native C3 molecule consists of two chains, C3-alpha and C3-beta. Small fragments breaking down from C3-alpha chain in serum and SF were reported to be related to OA severity. Little is known if C3-beta chain is involved in the pathogenesis. Method In this study, we evaluated these important areas by biochemical analyses of C3-alpha and C3-beta chains in both the SF and plasma of OA patients. Results Our results showed that C3-alpha and C3-beta levels in SF did not correlate with those in plasma, suggesting that synovial C3 is independently and locally produced, rather than being "leaked" from circulation. Synovial C3-beta but not C3-alpha levels correlated with pain, other OA symptoms, function in daily living, and sports/recreational activities. Plasma C3-beta levels only marginally correlated with pain, and plasma C3-alpha levels did not correlate with any of these OA symptoms. Conclusion We present first-hand evidence that the clinical symptoms of OA are mainly associated with C3 in the local SF rather than systemic circulation, suggesting local factors in the etiopathogenesis. Future local targeted therapies for pain management may be more effective and safer.