The primary source of synovial fluid inflammatory mediators is currently unknown and may include different tissues comprising the joint, including the synovium and articular cartilage. Prior work in a porcine model has demonstrated that anterior cruciate ligament (ACL) surgery leads to significant changes in early gene expression in the synovium and articular cartilage, which are the same whether concomitant ligament restoration is performed or not. In this study, 36 Yucatan minipigs underwent ACL surgery, and a custom multiplex assay was used to measure synovial fluid protein levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-12, MMP-13, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, GM-CSF, and TNFα in 18 animals at 1 and 4 weeks after surgery. Linear regressions were used to evaluate the relationships between synovial fluid protein levels and the previously reported gene expression levels in the articular cartilage and synovium from the same animal cohort. Synovial fluid levels of MMP-13 and IL-6 were significantly correlated with synovial gene expression (P=.003 and P<.001 respectively), while IL-1α levels were significantly correlated with articular cartilage gene expression (P=.037). The synovium may be an important source of MMP-13 and IL-6, and the articular cartilage may be an important source of IL-1α in post-surgical inflammation. In developing treatments for post-surgical inflammation, the synovium may therefore be a promising target for modulating inflammatory mediators such as MMP-13 and IL-6 in the synovial fluid.
Keywords: Inflammation; animal model; biomarkers; cartilage; knee; osteoarthritis-post traumatic; synovium.
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