Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanism
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 LP...
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BMJ Publishing Group
2025-07-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/11/3/e005622.full |
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| author | Kari K Eklund Caroline Ospelt Thomas Rauer Rodolfo Gómez Hans-Christoph Pape Kajetana Bevc Shipin Zhang Andres Pazos-Perez Ana Alonso-Perez David Fercher Sami Kauppinen Tuomas Frondelius Valentino Bruhin Gian Salzmann Mikko Arttu Jalmari Finnilä Marcy Zenobi Wong Goncalo Barreto |
| author_facet | Kari K Eklund Caroline Ospelt Thomas Rauer Rodolfo Gómez Hans-Christoph Pape Kajetana Bevc Shipin Zhang Andres Pazos-Perez Ana Alonso-Perez David Fercher Sami Kauppinen Tuomas Frondelius Valentino Bruhin Gian Salzmann Mikko Arttu Jalmari Finnilä Marcy Zenobi Wong Goncalo Barreto |
| author_sort | Kari K Eklund |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-52f59fd245754e309af65f0fb5b40974 |
| institution | DOAJ |
| issn | 2056-5933 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj-art-52f59fd245754e309af65f0fb5b409742025-08-20T03:17:52ZengBMJ Publishing GroupRMD Open2056-59332025-07-0111310.1136/rmdopen-2025-005622Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanismKari K Eklund0Caroline Ospelt1Thomas Rauer2Rodolfo Gómez3Hans-Christoph Pape4Kajetana Bevc5Shipin Zhang6Andres Pazos-Perez7Ana Alonso-Perez8David Fercher9Sami Kauppinen10Tuomas Frondelius11Valentino Bruhin12Gian Salzmann13Mikko Arttu Jalmari Finnilä14Marcy Zenobi Wong15Goncalo Barreto16Department of Rheumatology, Helsinki University Central Hospital, Helsinki, FinlandCenter of Experimental Rheumatology, University Hospital Zurich, Zürich, SwitzerlandDepartment of Traumatology, University Hospital Zurich, Zürich, SwitzerlandUniversity Hospital of Santiago de Compostela, Santiago de Compostela, SpainDepartment of Traumatology, University Hospital Zurich, Zürich, SwitzerlandD-HEST, ETH Zurich, Zürich, SwitzerlandD-HEST, ETH Zurich, Zürich, SwitzerlandUniversity Hospital of Santiago de Compostela, Santiago de Compostela, SpainUniversity Hospital of Santiago de Compostela, Santiago de Compostela, SpainD-HEST, ETH Zurich, Zürich, SwitzerlandResearch Group of Medical Imaging, Physics and Technology, University of Oulu, Oulu, FinlandResearch Group of Medical Imaging, Physics and Technology, University of Oulu, Oulu, FinlandSchulthess Klinik, Zürich, SwitzerlandSchulthess Klinik, Zürich, SwitzerlandResearch Group of Medical Imaging, Physics and Technology, University of Oulu, Oulu, FinlandD-HEST, ETH Zurich, Zürich, SwitzerlandClinicum, University of Helsinki Faculty of Medicine, Helsinki, FinlandObjective 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.https://rmdopen.bmj.com/content/11/3/e005622.full |
| spellingShingle | Kari K Eklund Caroline Ospelt Thomas Rauer Rodolfo Gómez Hans-Christoph Pape Kajetana Bevc Shipin Zhang Andres Pazos-Perez Ana Alonso-Perez David Fercher Sami Kauppinen Tuomas Frondelius Valentino Bruhin Gian Salzmann Mikko Arttu Jalmari Finnilä Marcy Zenobi Wong Goncalo Barreto Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanism RMD Open |
| title | Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanism |
| title_full | Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanism |
| title_fullStr | Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanism |
| title_full_unstemmed | Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanism |
| title_short | Evaluating the role of lipopolysaccharides in the joint: fibronectin as a novel protective mechanism |
| title_sort | evaluating the role of lipopolysaccharides in the joint fibronectin as a novel protective mechanism |
| url | https://rmdopen.bmj.com/content/11/3/e005622.full |
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