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CD248\/endosialin is expressed by fibroblasts in the synovium, is highly up\u2010regulated during inflammation, and has been proposed as a potential therapeutic target. This study aimed to map the expression of CD248 in disease\u2010associated fibroblast states and to elucidate its role in pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Molecular profiling of stromal cells from healthy and arthritic (K\/BxN serum transfer\u2010induced arthritis) wildtype (\n                      <jats:italic>Cd248<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>+\/+<\/jats:italic>\n                      <\/jats:sup>\n                      ) and\n                      <jats:italic>Cd248<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice was performed using 3\u2032 single\u2010cell RNA sequencing. Arthritis trajectory and severity were assessed in both genotypes by clinical scoring, microcomputed tomography (micro\u2010CT), histology, and flow cytometry of dissociated synovium. Additionally, healthy mice of each genotype were aged to 20 months and hind limbs assessed by micro\u2010CT and histology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Cells expressing high levels of\n                      <jats:italic>Cd248<\/jats:italic>\n                      also express the \u201c\n                      <jats:italic>Pi16<\/jats:italic>\n                      \u201d fibroblast progenitor gene signature. Genetic deletion of\n                      <jats:italic>Cd248<\/jats:italic>\n                      in mice altered the differentiation trajectory of these progenitors, predisposing them to become destructive lining layer fibroblasts. Consequently,\n                      <jats:italic>Cd248<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      arthritic mice showed a phenotype of rapid, extensive bone damage. Unexpectedly, bone erosion and resultant deformity were also observed in aged\n                      <jats:italic>Cd248<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice in the absence of an inflammatory stimulus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Genetic deletion of\n                      <jats:italic>Cd248<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      results in uncoupling of inflammation and damage due to dysregulated fibroblast progenitor differentiation. Our data suggest that the high levels of CD248 expression seen on synovial fibroblasts provides a protective brake that attenuates bone damage by preventing the polarization of emergent fibroblasts toward a destructive phenotype. Therapeutic targeting of this protein may exacerbate disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70327","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:56:31Z","timestamp":1788771391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>CD248<\/scp>\n                    \/Endosialin Regulates Synovial Fibroblast State to Control Coupling of Inflammation and Bone Damage in Murine Models of Immune\u2010Mediated Inflammatory Arthritis and Aging"],"prefix":"10.1002","author":[{"given":"Samuel","family":"Kemble","sequence":"first","affiliation":[{"name":"Department of Inflammation and Ageing School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham  United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7136-2779","authenticated-orcid":false,"given":"Corinna","family":"Wehmeyer","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham  United Kingdom"},{"name":"Institute of Musculoskeletal Medicine, University of M\u00fcnster  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Ageing School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham  United Kingdom"},{"name":"School of Computer Science, University of Birmingham  United Kingdom"},{"name":"School of Engineering and Physical Sciences, University of Lincoln  United 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