{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T07:06:59Z","timestamp":1784790419033,"version":"3.55.0"},"reference-count":157,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T00:00:00Z","timestamp":1698796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormal activation of multiple immune and non-immune cells and proinflammatory factors mediate the development of joint inflammation in genetically susceptible individuals. Although specific environmental factors like smoking and infections are associated with disease pathogenesis, until now, we did not know the autoantigens and arthritogenic factors that trigger the initiation of the clinical disease. Autoantibodies recognizing specific post-translationally modified and unmodified antigens are generated and in circulation before the onset of the joint disease, and could serve as diagnostic and prognostic markers. The characteristic features of autoantibodies change regarding sub-class, affinity, glycosylation pattern, and epitope spreading before the disease onset. Some of these antibodies were proven to be pathogenic using animal and cell-culture models. However, not all of them can induce disease in animals. This review discusses the aberrant activation of major immune and non-immune cells contributing to joint inflammation. Recent studies explored the protective effects of extracellular vesicles from mesenchymal stem cells and bacteria on joints by targeting specific cells and pathways. Current therapeutics in clinics target cells and inflammatory pathways to attenuate joint inflammation and protect the cartilage and bones from degradation, but none cure the disease. Hence, more basic research is needed to investigate the triggers and mechanisms involved in initiating the disease and relapses to prevent chronic inflammation from damaging joint architecture.<\/jats:p>","DOI":"10.3390\/ijms242115883","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T11:51:43Z","timestamp":1698839503000},"page":"15883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Aberrant Activation of Immune and Non-Immune Cells Contributes to Joint Inflammation and Bone Degradation in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-8197","authenticated-orcid":false,"given":"Kutty Selva","family":"Nandakumar","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden"},{"name":"Department of Environmental and Biosciences, Halmstad University, 30118 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1482-1490","authenticated-orcid":false,"given":"Isabella","family":"Wingbro \u00c5gren","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biosciences, Halmstad University, 30118 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe Fuwen","family":"Bejmo","sequence":"additional","affiliation":[{"name":"Department of Environmental and Biosciences, Halmstad University, 30118 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/art.1780380106","article-title":"Validity and reliability of the twenty-eight-joint count for the assessment of rheumatoid arthritis activity","volume":"38","author":"Smolen","year":"1995","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1097\/BOR.0b013e3283454124","article-title":"New therapies in the management of rheumatoid arthritis","volume":"23","author":"Buch","year":"2011","journal-title":"Curr. 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