Synovial Fluid Biomarkers in the Osteoarthritic Knee: Differences in Concentration with Progression of Radiographic Severity

OBJECTIVES: The purpose of the current study was to analyze the synovial fluid concentrations of known inflammatory biomarkers in the setting of symptomatic osteoarthritis (OA) of the knee and assess for any differences in biomarker concentrations based on the extent of radiographic disease. METHODS: Patients presenting with knee complaints were invited to provide synovial fluid samples from the symptomatic knee during their initial office visit. For this study, a subset of patients with OA was analyzed. The concentration of 16 synovial fluid biomarkers was measured, including TIMP-1, TIMP-2, TIMP-3, MMP-13, IL-6, MCP-1, MIP-1β, VEGF, bFGF, eotaxin, IL-1Ra, MMP-1, MMP-3, MMP-9, RANTES, and TSG-6. Samples were analyzed using a multiplex magnetic bead immunoassay. Patients were divided into a low-grade OA group (K-L ≤ 2 or OARSI ≤ 1) or a high-grade cartilage OA group (K-L ≥ 3 or OARSI ≥ 2). RESULTS: 101 patients were included in this analysis. There was a significant difference in MIP-1β (p=0.025) and bFGF (p=0.015) concentrations between OARSI grade groups. Patients with high-grade joint space narrowing had significantly greater concentrations of MIP-1β (p=0.022) and bFGF (p=0.003). There was a significant difference in MIP-1β concentration between K-L grade groups (p=0.013). Patients in the high-grade K-L group had a significantly greater concentration of MIP-1β (p=0.020). CONCLUSIONS: The synovial fluid concentrations of two synovial fluid biomarkers were found to differ significantly based on the extent of radiographic OA present. MIP-1β is a pro-inflammatory growth factor known to induce the synthesis of other inflammatory factors including interleukins and TNF-α. bFGF is a growth factor that is known to promote chondrogenesis, angiogenesis, wound healing, and granulation tissue formation. Continued study of synovial fluid biomarkers in the setting of symptomatic OA may improve our understanding of the pathogenesis of disease and identify treatment targets in an attempt to halt disease progression.