Macrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Joints

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dc.contributor.authorMenarim, Bruno C.en
dc.contributor.authorGillis, Kiersten H.en
dc.contributor.authorOliver, Andreaen
dc.contributor.authorNgo, Yingen
dc.contributor.authorWerre, Stephen R.en
dc.contributor.authorBarrett, Sarah H.en
dc.contributor.authorRodgerson, Dwayne H.en
dc.contributor.authorDahlgren, Linda A.en
dc.contributor.departmentLarge Animal Clinical Sciencesen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-01-20T18:36:09Zen
dc.date.available2021-01-20T18:36:09Zen
dc.date.issued2020-11-26en
dc.description.abstractSynovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial for joint homeostasis (M2-like phenotype), but induce inflammation (M1-like) when regulatory functions become overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized; however, comparative knowledge of their phenotypes during health and disease is paramount for developing targeted treatments. This study compared patterns of macrophage activation in healthy and osteoarthritic equine synovium and correlated histology with cytokine/chemokine profiles in synovial fluid. Synovial histology and immunohistochemistry for M1-like (CD86), M2-like (CD206, IL-10), and pan macrophage (CD14) markers were performed on biopsies from 29 healthy and 26 osteoarthritic equine joints. Synovial fluid cytokines (MCP-1, IL-10, PGE(2), IL-1 beta, IL-6, TNF-alpha, IL-1ra) and growth factors (GM-CSF, SDF-1 alpha+beta, IGF-1, and FGF-2) were quantified. Macrophage phenotypes were not as clearly defined in vivo as they are in vitro. All macrophage markers were expressed with minimal differences between OA and normal joints. Expression for all markers increased proportionate to synovial inflammation, especially CD86. Synovial fluid MCP-1 was higher in osteoarthritic joints while SDF-1 and IL-10 were lower, and PGE(2) concentrations did not differ between groups. Increased CD14/CD86/CD206/IL-10 expression was associated with synovial hyperplasia, consistent with macrophage recruitment and activation in response to injury. Lower synovial fluid IL-10 could suggest that homeostatic mechanisms from synovial macrophages became overwhelmed preventing inflammation resolution, resulting in chronic inflammation and OA. Further investigations into mechanisms of arthritis resolution are warranted. Developing pro-resolving therapies may provide superior results in the treatment of OA.en
dc.description.notesThis study was supported by the American College of Veterinary Surgeons Foundation.en
dc.description.sponsorshipAmerican College of Veterinary Surgeons Foundationen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fvets.2020.568756en
dc.identifier.eissn2297-1769en
dc.identifier.other568756en
dc.identifier.pmid33324696en
dc.identifier.urihttp://hdl.handle.net/10919/101974en
dc.identifier.volume7en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectjoint homeostasisen
dc.subjectosteoarthiritisen
dc.subjectsynovitisen
dc.subjectinflammatioinen
dc.subjectactivationen
dc.subjectpolarizationen
dc.titleMacrophage Activation in the Synovium of Healthy and Osteoarthritic Equine Jointsen
dc.title.serialFrontiers in Veterinary Scienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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