Human aggrecanase generated synovial fluid fragment levels are elevated directly after knee injuries due to proteolysis both in the interglobular and chondroitin sulfate domains
Struglics A, Hansson M, & Lohmander LS. Osteoarthritis Cartilage. 2011; 19: 1047-1057: doi: 10.1016/j.joca.2011.05.006
Knee injuries have been implicated as catalysts for the development of osteoarthritis (OA). Several studies have previously reported biochemical changes following a knee injury that may increase the risk for OA. This study focuses on aggrecanase, a major protein that breaks down structural cartilage molecules (aggrecan) into fragments that can be found in the synovial (joint) fluid. The purpose of this study was to examine aggrecan fragments in synovial fluid from patients with knee injury (35 knees with acute and 35 knees with chronic injuries) compared to 10 healthy patients’ knees. Knee injuries were defined as any of the following: anterior cruciate ligament tear, meniscus tear, collateral ligament tear, osteochondral fracture, and were categorized as acute if the injury occurred 0 to 12 weeks prior to fluid sampling (the average was 2.2 weeks) or chronic if the injury occurred ≥ 52 weeks before sampling (the average was 278 weeks). The synovial fluid samples were analyzed utilizing a technique that can identify various types of aggrecan fragments. All measures of aggrecan fragments were significantly higher in the acute knee injury group than in the control group. The chronic knee injury group had some similar measures to the control group but there was still evidence of aggrecan turnover. Some of the fragments had very high specificity (specificity: not falsely diagnosing a healthy patient) and sensitivity (sensitivity: positively diagnose a patient who has pathology). There were no differences between genders.
This study is important because it demonstrates that there are clear biochemical changes of aggrecanase after a knee injury. While some of the measures return to normal within 2 years of injury, there are some that remain elevated long after, indicating that an injured knee may never actually return to “normal” biochemically. The authors note that the fragments present after an injury are similar to the patterns we observe in knees with OA. This coupled with the altered biomechanics that follow knee injuries could expedite the premature development of OA. It would be interesting if future studies investigated differences among the knee injuries (e.g., meniscus vs. ACL) or monitored any changes in these markers following interventions. These early biochemical changes after an injury may indicate that an intervention to prevent OA may need to occur during this time frame, as opposed to when structural changes and symptoms start to occur. If this is the case, then sports medicine clinicians are in an ideal position to intervene early and help prevent long-term health issues associated with OA (e.g., pain, decreased quality of life, increased disability). Biomarkers may serve as the means to successfully identify and manage early OA.
Written by: Nicole Cattano
Reviewed by: Jeffrey Driban