{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:05:54Z","timestamp":1784786754810,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the mechanisms underlying the bone-sparing effects of the anti-TNF antibody adalimumab in rheumatoid arthritis (RA) by examining synovial tissue and its direct effect on osteoblasts and osteoclasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Paired synovial biopsies from 12 patients with RA were obtained before and 8 weeks after initiation of adalimumab. Immune-cell infiltrates (CD163\n                      <jats:sup>+<\/jats:sup>\n                      macrophages, CD3\n                      <jats:sup>+<\/jats:sup>\n                      lymphocytes) and expression of osteoprotegerin (OPG), receptor activator of nuclear factor \u03baB (RANK), and its ligand (RANKL) were assessed by immunohistochemistry.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , the effect of adalimumab on RANKL and OPG expression in SaOS-2 cells (\u00b1\u00a0TNF-\u03b1) was evaluated by western blotting. Its effect on osteoclastogenesis and bone resorption were examined using CD14\n                      <jats:sup>+<\/jats:sup>\n                      monocyte-derived macrophages cultured with RANKL and M-CSF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Adalimumab treatment led to a marked clinical improvement, with median DAS28 decreasing from 5.4 to 3.1. Semiquantitative analysis of synovial biopsies revealed a significant decrease in CD163\n                      <jats:sup>+<\/jats:sup>\n                      macrophages, while CD3\n                      <jats:sup>+<\/jats:sup>\n                      T-cells remained unchanged. The RANKL\/OPG ratio decreased significantly, which was accompanied by increased OPG expression in synovial tissue.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , adalimumab significantly decreased RANKL expression and the RANKL: OPG ratio in TNF-\u03b1 primed SaOS-2 cells, while also modulating pro-osteoclastogenic cytokines. In osteoclast assays, adalimumab inhibited macrophage-derived osteoclast differentiation and suppressed bone resorption under both low and high RANKL conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Adalimumab decreased synovial macrophage infiltration while it modulates pro-osteoclastogenic cytokines and inhibits osteoclastogenesis. These combined effects explain how TNF-\u03b1 blockade ameliorates joint inflammation and prevents structural damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1866519","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:38:40Z","timestamp":1784785120000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TNF-\u03b1 blockade with adalimumab restores bone metabolism in rheumatoid arthritis by regulating cytokines and inflammatory cell infiltration"],"prefix":"10.3389","volume":"17","author":[{"given":"Akilan","family":"Krishnamurthy","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, and Center for Molecular Medicine (CMM)","place":["Stockholm, 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