Relationship between synovial fluid biomarkers of articular cartilage metabolism and the patient's perspective of outcome depends on the severity of articular cartilage damage following ACL trauma

Abstract

Anterior cruciate ligament (ACL) trauma often occurs in combination with injury to the articular cartilage of the knee, this can result in earlier radiographic evidence of post traumatic osteoarthritis (OA) of the knee compared to the contralateral, ACL intact knee; however, the biomechanical and biological mechanisms associated with the onset and progression of this disease are not understood. We sought to gain insight into the mechanisms by determining the relationship between articular cartilage injury associated with ACL trauma and the expression of synovial fluid biomarkers of articular cartilage metabolism, and to evaluate the relationship between these biomarkers and the patient's perspective of the outcomes. Synovial fluid samples were acquired from 39 ACL injured subjects at an average of 10 weeks after injury, and 32 control subjects with normal knees (documented with clinical exam and MRI assessment). Subjects in the ACL-injured group were classified as low-risk for future OA if they displayed an International Cartilage Repair Society (ICRS) Grade 2 articular cartilage lesion or less and high-risk for future OA if they had an ICRS Grade 3A articular cartilage lesion. The patient's perspective of the injury was evaluated with the Knee Injury and Osteoarthritis Outcomes Score (KOOS). There were no significant differences in mean concentrations of the markers of type II collagen metabolism (CPII, C2C, and C1,2C) or the aggrecan breakdown Alanine-Arginine-Glycine-Serine (ARGS) -fragment between control subjects and the subjects in the low- and high-risk groups (p-value range: 0.80-0.43). Associations between ARGS-aggrecan concentration and KOOS subscales of symptoms and pain were significantly different between the low- and high-risk groups (p = 0.03 and p = 0.01, respectively). Likewise, there was strong evidence in support of an association between the markers of type II collagen metabolism (C1,2C and CPII concentrations) and the KOOS subscale of pain between the low- and high-risk groups (p = 0.051 and 0.077, correspondingly). In ACL injured subjects with concomitant Grade 3A articular cartilage injuries, concentrations of synovial fluid ARGS-aggrecan were directly associated with improvements in KOOS symptoms and pain. These findings suggest the possible involvement of ARGS-aggrecan in a localized tissue repair response involving an increase in aggrecan turnover following severe knee trauma.