Boundary lubricants in osteoarthritic synovial fluid
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Osteoarthritis (OA) is a degenerative joint disease characterised among others by the progressive loss of articular cartilage. Lubricin, hyaluronic acid (HA) and surface-active phospholipids contribute to the boundary lubrication provided by synovial fluid (SF). During OA, alterations in the concentrations of lubricin and HA impair the boundary lubricating ability of SF and may lead to increased friction and ultimately greater cartilage damage. In this line, the main hypothesis of the current study was that OA SF contains altered amounts of individual PL species, which might contribute to cartilage destruction during OA, and that these alterations are dependent on the stage of the disease. Before starting the experiments, approval by the University ethics commission and the written informed consent of the patients were obtained. Qualitative and quantitative analyses of all phospholipids (PL) species were performed using electrospray ionization mass spectrometry (ESI-MS/MS) for human SF from healthy, rheumatoid arthritic (RA) and OA knee joints at different stages of the disease. Moreover, healthy and OA canine SF were also analysed in order to evaluate whether a canine model of OA reflects composition of PL species as found in human. In addition, the protein and mRNA expression pattern of surfactant proteins (SP-A, -D) was obtained in joint cells and SF.The results of our lipidomic study provide for the first time a detailed overview of all PL species being present in human SF. Our analyses of SF indicate differences between healthy, OA and RA SF. Interestingly, SF from late stage of OA exhibited significantly higher concentrations of most of PL species when compared with healthy SF. More importantly, we provide first evidence that significant differences in PL composition exist between early and late stage of OA indicating, that PL composition of SF can serve as biomarker to distinguish between stages of OA. Moreover, the results obtained from human were confirmed by analysis of SF from canine model of OA. Our results also indicate a possible pathologic function of PL in the development of OA as based on their role in the boundary lubrication of joints as well as their biological activities. In addition, we provide several experimental proofs that human SF does not contain SP-A and -D.In conclusion, our results support the hypothesis that alterations in composition and concentrations of PL species may also contribute to cartilage destruction during OA. Moreover, the specific PL pattern reflects stages of the disease. Hence, analysis of the SF lipidome can serve as a novel useful tool for diagnosis and prognosis of OA. Our data also indicate that surfactant proteins do not play any role in the boundary lubrication of joints.Verknüpfung zu Publikationen oder weiteren Datensätzen
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Giessen : VVB Laufersweiler