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Here, we found that the levels of\n microRNA<\/jats:styled-content>\n (\n miR<\/jats:styled-content>\n )\u2010103a\u20103p were decreased markedly in the inflamed synovial tissues of patients with\n RA<\/jats:styled-content>\n compared with osteoarthritis (\n OA<\/jats:styled-content>\n ) or healthy control subjects. Further studies uncovered that\n miR<\/jats:styled-content>\n \u2010103a\u20103p was significantly downregulated by\n TNF<\/jats:styled-content>\n \u2010\u03b1\/\n IL<\/jats:styled-content>\n \u20101\u03b2 in\n RA<\/jats:styled-content>\n fibroblast\u2010like synoviocytes (\n FLSs<\/jats:styled-content>\n ) through an\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n \u2013dependent manner via the de novo produced transcription factor Yin Yang 1 (\n YY1<\/jats:styled-content>\n ). In addition, downregulation of\n miR<\/jats:styled-content>\n \u2010103a\u20103p in\n FLSs<\/jats:styled-content>\n promoted\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n signaling pathway activation, inflammatory cytokines secretion, and bone marrow\u2010derived monocytes (\n BMMs)<\/jats:styled-content>\n cells differentiation into osteoclasts, whereas ectopic expression of\n miR<\/jats:styled-content>\n \u2010103a\u20103p had the opposite effects. Notably,\n miR<\/jats:styled-content>\n \u2010103a\u20103p was downregulated thousands of times in the sera of\n RA<\/jats:styled-content>\n patients and\n CIA<\/jats:styled-content>\n mice, while the blockade of\n TNF<\/jats:styled-content>\n \u2010\u03b1 with infliximab greatly recovered its levels in\n RA<\/jats:styled-content>\n patients in sustained remission. Consistently, rescue of\n miR<\/jats:styled-content>\n \u2010103a\u20103p expression by an\n agomiR<\/jats:styled-content>\n potently ameliorated inflammatory responses and bone erosion in\n CIA<\/jats:styled-content>\n mice. Mechanistically, mitogen\u2010activated protein kinase kinase kinase 7 (\n MAP3K7<\/jats:styled-content>\n ) and Dickkopf\u2010related protein 1 (\n DKK1<\/jats:styled-content>\n ) were identified as the direct targets of\n miR<\/jats:styled-content>\n \u2010103a\u20103p, by which it exerts the effects on synovial inflammation and cartilage bone destruction. Taken together,\n miR<\/jats:styled-content>\n \u2010103a\u20103p mediates\n TNF<\/jats:styled-content>\n \u2010triggered synovial inflammation and joint bone destruction via targeting\n MAP3K7<\/jats:styled-content>\n and\n DKK1<\/jats:styled-content>\n ; it thus serves as a candidate target for\n RA<\/jats:styled-content>\n treatment.\n <\/jats:p>","DOI":"10.1096\/fj.202501452r","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T16:10:36Z","timestamp":1753287036000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["TNF<\/scp>\n \u2010\u03b1 Promotes Synovial Inflammation and Cartilage Bone Destruction in Rheumatoid Arthritis via\n NF<\/scp>\n \u2010\n \u03baB<\/scp>\n \/\n YY1<\/scp>\n \/\n miR<\/scp>\n \u2010103a\u20103p 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