{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:17:42Z","timestamp":1793852262971,"version":"4.6.1"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T00:00:00Z","timestamp":1740700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Rheumatoid arthritis and periodontitis are comorbidities that share mutual pathways. IL-1\u03b2 is a pro-inflammatory cytokine that plays a crucial role in both diseases. One of the treatment options for rheumatoid arthritis is the use of an IL-1 receptor antagonist (IL-1RA) such as anakinra. Anakinra tempers the disease by decreasing bone resorption and it could possibly stimulate bone formation. Here, we investigate the effect of anakinra in a periodontal disease setting on osteoclastogenesis by co-culturing periodontal ligament fibroblasts (PDLFs) and peripheral blood mononuclear cells (PBMCs) that contain monocytes, a source of osteoclast precursors, as well as by culturing PBMCs alone. The effect of anakinra on PDLF-mediated osteogenesis was studied under mineralization conditions. To mimic a chronic infection such as that prevalent in periodontitis, 10 ng\/mL of IL-1\u03b2 was added either alone or with 10 \u00b5g\/mL of anakinra. Osteoclastogenesis experiments were performed using co-cultures of PDLF and PBMCs and PBMCs only. Osteoclastogenesis was determined through the formation of multinucleated cells in co-cultures of PDLF and PBMCs, as well as PBMCs alone, at day 21, and gene expression through qPCR at day 14. Osteogenesis was determined by measuring alkaline phosphatase activity (ALP) per cell at day 14. Anakinra is effective in downregulating IL-1\u03b2 mediated leukocyte clustering and osteoclastogenesis in the co-cultures of both PDLF and PMBCs and PBMCs alone. Gene expression analysis shows that IL-1\u03b2 increases the expression of the osteoclastogenic marker RANKL and its own expression. This higher expression of IL-1\u03b2 at the RNA level is reduced by anakinra. Moreover, IL-1\u03b2 downregulates OPG expression, which is upregulated by anakinra. No effects of anakinra on osteogenesis were seen. Clinically, these findings suggest that anakinra could have a beneficial systemic effect on periodontal breakdown in rheumatoid arthritis patients taking anakinra.<\/jats:p>","DOI":"10.3390\/biology14030250","type":"journal-article","created":{"date-parts":[[2025,2,28]],"date-time":"2025-02-28T10:46:46Z","timestamp":1740739606000},"page":"250","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["IL-1 Receptor Antagonist Anakinra Inhibits the Effect of IL-1\u03b2- Mediated Osteoclast Formation by Periodontal Ligament Fibroblasts"],"prefix":"10.3390","volume":"14","author":[{"given":"Elizabeth","family":"Steemers","sequence":"first","affiliation":[{"name":"Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Gustav Mahlerlaan 3004, 1081 LH Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wael M. I.","family":"Talbi","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Gustav Mahlerlaan 3004, 1081 LH Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanda M. A.","family":"Hogervorst","sequence":"additional","affiliation":[{"name":"Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Gustav Mahlerlaan 3004, 1081 LH Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6649-374X","authenticated-orcid":false,"given":"Ton","family":"Schoenmaker","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Gustav Mahlerlaan 3004, 1081 LH Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-5172","authenticated-orcid":false,"given":"Teun J.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Gustav Mahlerlaan 3004, 1081 LH Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/prd.12297","article-title":"The role of inflammation and genetics in periodontal disease","volume":"83","author":"Loos","year":"2020","journal-title":"Periodontology 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jbspin.2010.04.015","article-title":"Rheumatoid arthritis and periodontal disease","volume":"77","author":"Berthelot","year":"2010","journal-title":"Jt. 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