Abstract
Abstract Peptidoglycan (PG) is a potent inflammatory mediator. We have previously demonstrated that PG is present in the synovial tissue of osteoarthritis (OA) patients but its role in OA inflammation remains unknown. We hypothesized that PG in synovial tissue drives inflammation in OA. Intraoperative synovial tissue and synovial fluid samples were obtained from 56 consecutive patients with OA, with no prior history of infection. PG in synovial tissue was detected by immunohistochemical (IHC) staining of serial sections of 10 mm2 of tissue with anti-PG antiserum. PG was found in 33/56 (59%) of the tissue samples using IHC, with a median of eight PG occurrences per 10 mm2 in PG-positive samples. Tissue inflammation and fibrosis were assessed by histopathology. Cellular localization was further characterized in three PG-positive tissue samples by immunofluorescent microscopy (IFM). PG was localized to cells demonstrating mononuclear and fibroblastic morphology primarily in and around areas of vascularization and inflammation. CD68+ macrophages and to a lesser degree CD90+ synovial sublining fibroblasts. In multiplex assay analysis of synovial fluid cytokine levels, IL-6 and PG abundance were positively correlated. Fibroblasts and macrophages stimulated with PG in vitro secreted high levels of innate cytokines, paricularly IL-6 when measured by supernatant cytokine quantification. Together these data support the hypothesis that PG in synovial tissue drives joint inflammation in OA.
Published Version
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