Cheng TH, et al. - Investigators tried to find out whether knee synovial fluid complement C3-β chain levels correlate with clinical symptoms of knee osteoarthritis. These important areas were examined by biochemical analyses of C3-α and C3-β chains in both the synovial fluid (SF) and plasma of OA patients. The data indicated that C3-α and C3-β levels in SF did not associate with those in plasma, implying that synovial C3 is independently and locally produced, rather than being “leaked” from circulation. They recorded that synovial C3-β but not C3-α levels associated with pain, other OA symptoms, function in daily living, and sports/recreational activities. The first-hand evidence was found that the clinical symptoms of OA are mainly associated with C3 in the local SF rather than systemic circulation, implying local factors in the etiopathogenesis. For pain management, future local targeted therapies may be more effective and safer.