Kajetana Bevc, Shipin Zhang, Andres Pazos-Perez, Ana Alonso-Perez, David Fercher, Sami Kauppinen, Tuomas Frondelius, Valentino Bruhin, Gian Salzmann, Thomas Rauer, Hans-Christoph Pape, Mikko Arttu Jalmari Finnilä, Caroline Ospelt, Rodolfo Gomez, Kari K Eklund, Marcy Zenobi Wong, Goncalo Barreto
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引用次数: 0
Abstract
Objective: To investigate the presence and bioactivity of lipopolysaccharides (LPS) in synovial fluid (SF) of osteoarthritis (OA) patients and elucidate mechanisms modulating their inflammatory potential.
Methods: SF samples from 56 OA, 7 rheumatoid arthritis and 39 trauma patients were analysed for LPS concentration and bioactivity. Lipid A composition was assessed using liquid chromatography-mass spectrometry (LC-MS). In a rat model, LPS was administered systemically for 32 days to evaluate its impact on joint degeneration. The interaction between LPS and synovial proteins, particularly fibronectin (Fn), was examined through in vitro assays and a 3D synovial membrane model.
Results: LPS was detected in all SF samples with comparable concentrations and lipid A profiles across all groups. LC-MS measurements indicated higher LPS levels than those obtained from standard endotoxin assays, suggesting limitations in conventional detection methods. Despite elevated LPS presence, bioactivity assays revealed minimal proinflammatory responses, implying the existence of intrinsic SF factors neutralising LPS. In vivo, prolonged systemic LPS exposure did not induce OA-like changes in rat joints. Notably, LPS colocalised with Fn in the synovial membrane, and Fn binding attenuated LPS bioactivity and hindered its migration in vitro.
Conclusions: LPS is prevalent in SF across various joint conditions but exhibits low bioactivity, indicating it is not a primary driver of joint inflammation. Fn plays a crucial role in sequestering and neutralising LPS within the synovial environment, offering a protective mechanism against LPS-induced inflammation. These findings underscore the need for accurate LPS measurement techniques and suggest potential therapeutic targets for modulating joint inflammation.
期刊介绍:
RMD Open publishes high quality peer-reviewed original research covering the full spectrum of musculoskeletal disorders, rheumatism and connective tissue diseases, including osteoporosis, spine and rehabilitation. Clinical and epidemiological research, basic and translational medicine, interesting clinical cases, and smaller studies that add to the literature are all considered.