Abstract
ObjectiveEvidence is accumulating that synovial tissue plays an active role in osteoarthritis (OA), however, exact understanding of its contribution is lacking. In order to further elucidate its role in the OA process, we aimed to identify the secretion pattern of soluble mediators by synovial tissue and to assess its ability to initiate cartilage degeneration.MethodsSynovial tissue explants (STEs) obtained from donors without history of OA (n = 8) or from end stage OA patients (n = 16) were cultured alone or together with bovine cartilage explants in the absence or presence of IL-1α. The secretion of 48 soluble mediators was measured and the effect on glycosaminoglycan (GAG) release and matrix metalloproteinase (MMP) activity was determined.ResultsNormal and OA STEs secreted comparable levels of almost all measured soluble mediators. However, in the presence of IL-1α these mediators were less secreted by OA than by normal STEs of which 15 differed significantly (p<0.01). No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected.ConclusionsUnexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients. The effects could be the result of prolonged exposure to an inflammatory environment in OA development. Further understanding of the pro-inflammatory and inflammation resolving mechanisms during disease progression in synovial tissue may provide valuable targets for therapy in the future.
Highlights
Osteoarthritis (OA) is one of the most frequently occurring rheumatic diseases
synovial tissue explants (STEs) Collection Synovium of the knee was obtained from post-mortem material of 8 donors with macroscopically healthy cartilage and no history of OA, or from material obtained during joint replacement surgery of 16 OA patients (OA STE) (Articular Engineering, Northbrook, USA)
Secretion of Soluble Mediators by STEs To assess differences between normal and OA STEs 48 soluble mediators were measured in the pooled supernatants
Summary
Osteoarthritis (OA) is one of the most frequently occurring rheumatic diseases. In Western populations OA is by far the most common form of joint disease, causing pain, loss of function and disability [1]. The main characteristic of the disease is progressive loss of articular cartilage, which is thought to be due to an imbalanced interplay between anabolic, anti-catabolic, anti- and pro-inflammatory and anti- and pro-apoptotic activities [2,3]. Numerous risk factors for OA have been identified, the exact etiology, pathogenesis and progression of this disease have yet to be determined [4]. As a consequence of the limited understanding of the disease complexity, no disease modifying treatments are currently available. The only existing therapeutic strategies are primarily aimed at reducing pain and improving joint function
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