Summary

While ACL and meniscal injuries resulted in a largely pro-inflammatory phenotype, more severe cartilage lesions were associated with a reduced presence of anti-inflammatory markers.

Abstract

Objectives: The aim of this study was to investigate if unique patterns of knee injury are associated with distinct synovial fluid biomarker profiles at the time of surgical intervention. This knowledge may improve our understanding of underlying pathophysiologic mechanisms and provide information of diagnostic and/or therapeutic significance.

Methods

Patients undergoing arthroscopic knee surgery were prospectively enrolled. Synovial fluid was aspirated from the operative knee before surgical incision and the concentrations of 10 biomarkers of interest (RANTES, IL-6, MCP-1, MIP-B, VEGF, TIMP-1, TIMP-2,IL-1RA, MMP-3, and bFGF) were measured by immunoassay. Patients with evidence of injury to articular cartilage, meniscus, and/or ACL were identified and included for subsequent analysis. Biomarker concentrations were log-normalized and standardized by Z-score. Principal component analysis (PCA) was performed using all 10 biomarker variables to reduce dimensionality, address multicollinearity, and extract key patterns. Principal components with eigenvalue > 1 were selected. Multivariable linear regression for each resulting principal component was performed with predictors age, sex, body mass index, ACL injury, meniscal injury, and Outerbridge grade.

Results

A total of 387 patients were included in the analysis, of which 176 (45.5%) had ACL rupture, 327 (84.5%) had meniscal injury, and 225 (58.1%) had cartilage injury. PCA yielded 3 principal components (PC1, PC2, PC3) that explained 66.9% of variance in biomarker data. PC1 was found with greater than expected loadings of VEGF, IL6, MMP-3, MIP-1B, MCP-1; PC2 with TIMP-1 and TIMP-2; and PC3 with RANTES, bFGF, and IL-1RA. Multivariable linear regression found ACL injury (p = 0.020, B = 0.315) and meniscal injury (p = 0.032 , B = 0.324) to be positively associated with PC1, Outerbridge grade to be negatively associated with PC2 (p < 0.025, B = - 0.083), and ACL injury to be positively associated with PC3 (p = 0.033, B = 0.288).

Conclusions

Cartilage lesions exhibited a synovial fluid inflammatory profile distinct from ACL and meniscal injury at the time of arthroscopic knee surgery in a broad multi-injury cohort. While ACL and meniscal injuries displayed a largely pro-inflammatory phenotype, more severe cartilage lesions were associated with a reduced presence of anti-inflammatory markers. Understanding the varying local responses to specific knee injuries may help guide a pathology-specific treatment in the effort to prevent the development of post-traumatic osteoarthritis.