Anterior Cruciate Ligament, Meniscal, and Cartilage Injuries Are Associated With Distinct Synovial Fluid Biomarker Profiles at the Time of Knee Arthroscopy

Abstract

Background: The knee’s inflammatory response to ligamentous, meniscal, and cartilage injuries is complex and incompletely understood, particularly in the setting of concomitant injuries. Recent research has highlighted the potential utility of synovial fluid biomarker analysis in identifying factors involved in the progression of posttraumatic osteoarthritis. Purpose: To investigate if unique patterns of knee injury are associated with distinct synovial fluid biomarker profiles at the time of surgical intervention. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patients undergoing arthroscopic knee surgery were prospectively enrolled and asked to complete the Lysholm Knee Scoring Scale and visual analog scale for pain preoperatively. Synovial fluid was aspirated from the operative knee before surgical incision, and the concentrations of 10 biomarkers of interest were quantified. Patients with intraoperative evidence of articular cartilage, meniscal, and/or anterior cruciate ligament (ACL) injury were identified and included for subsequent analysis. Biomarker concentrations were log-normalized and standardized. Principal component analysis (PCA) was performed using biomarker variables to reduce dimensionality and extract key patterns. Multivariable linear regression for each retained principal component (PC) was performed with the predictors of age, sex, body mass index, symptom duration, ACL injury, meniscal injury, and Outerbridge grade. A separate regression analysis was performed to assess relationships between PCs and patient-reported outcomes controlling for the same variables. Results: A total of 387 patients were included in the analysis, of whom 176 (45.5%) had ACL rupture, 327 (84.5%) had meniscal injury, and 225 (58.1%) had cartilage injury. PCA yielded 3 PCs (PC1, PC2, and PC3) that explained 66.9% of variance in biomarker data. PC1 was found with significant loadings of VEGF, IL-6, MMP-3, MIP-1β, and MCP-1; PC2 with TIMP-1 and TIMP-2; and PC3 with RANTES, bFGF, and IL-1RA. Multivariable linear regression found ACL injury ( P = .014; β = .164) and meniscal injury ( P = .029; β = .118) to be positively associated with PC1, Outerbridge grade to be negatively associated with PC2 ( P = .041; β = –.132), and ACL injury to be positively associated with PC3 ( P = .035; β = .141). PC1 was associated with a worse preoperative Lysholm score ( P = .001; β = –.199). Conclusion: Cartilage lesions exhibited a synovial fluid inflammatory profile distinct from ACL and meniscal injury at the time of knee arthroscopy. While ACL and meniscal injuries displayed a pro-inflammatory phenotype, more severe cartilage lesions were associated with a reduced presence of anti-inflammatory markers. The pro-inflammatory phenotype also independently correlated with worse baseline knee function. These findings contribute to the understanding of the pathophysiology of ligamentous, meniscal, and cartilage injuries and may aid in the identification of pathology-specific treatments to help alter the natural history of disease.