{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:31:37Z","timestamp":1792812697673,"version":"4.5.0"},"reference-count":24,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"UCB Pharma"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2020,6,25]]},"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec id=\"s1\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Interleukin (IL)-17 signalling has been shown to be a key regulator of disease in ankylosing spondylitis (AS) with several IL-17 blockers currently clinically approved. Despite this, the role of IL-17 in bone pathology is poorly understood. This study aimed to investigate IL-17 signalling in the context of pathological bone formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"s2\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A biomimetic human periosteum-derived cell (hPDC) model of osteogenic differentiation was used in combination with recombinant IL-17 cytokines, T-cell supernatants or serum from patients with AS. IL-17A, IL-17F and bimekizumab monoclonal antibodies were used to block IL-17 cytokine action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"s3\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Recombinant IL-17A and IL-17F are pro-osteogenic with respect to hPDC differentiation. T helper 17 or \u03b3\u03b4-T cell supernatants also potently stimulated in vitro bone formation, which was blocked deeper by dual inhibition of IL-17A and IL-17F than by neutralisation of IL-17A or IL-17F individually. Osteogenic blockade may be due to an increase in expression of the Wnt antagonist\n                      <jats:italic>DKK1<\/jats:italic>\n                      . Interestingly, osteocommitment was also induced by serum obtained from patients with AS, which was also abrogated by dual neutralisation of IL-17A and IL-17F.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"s4\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data show for the first time that IL-17A and IL-17F enhance in vitro osteogenic differentiation and bone formation from hPDCs, inhibition of which may offer an attractive therapeutic strategy to prevent pathological bone formation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/rmdopen-2020-001306","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T17:40:59Z","timestamp":1595958059000},"page":"e001306","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["Dual neutralisation of IL-17F and IL-17A with bimekizumab blocks inflammation-driven osteogenic differentiation of human periosteal cells"],"prefix":"10.1136","volume":"6","author":[{"given":"Mittal","family":"Shah","sequence":"first","affiliation":[{"name":"UCB Pharma, Slough, UK"},{"name":"Division of Surgery and Interventional Science, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher","family":"Maroof","sequence":"additional","affiliation":[{"name":"UCB Pharma, Slough, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Gikas","sequence":"additional","affiliation":[{"name":"Royal National Orthopaedic Hospital Stanmore, Stanmore, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayatri","family":"Mittal","sequence":"additional","affiliation":[{"name":"Royal National Orthopaedic Hospital Stanmore, Stanmore, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Keen","sequence":"additional","affiliation":[{"name":"Royal National Orthopaedic Hospital Stanmore, Stanmore, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Baeten","sequence":"additional","affiliation":[{"name":"UCB Pharma, Slough, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stevan","family":"Shaw","sequence":"additional","affiliation":[{"name":"UCB Pharma, Slough, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3974-8895","authenticated-orcid":false,"given":"Scott J","family":"Roberts","sequence":"additional","affiliation":[{"name":"UCB Pharma, Slough, UK"},{"name":"Division of Surgery and Interventional Science, University College London, London, UK"},{"name":"Department of Comparative Biomedical Sciences, Royal Veterinary College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"2025090312091176000_6.2.e001306.1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2642"},{"key":"2025090312091176000_6.2.e001306.2","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/art.40770","article-title":"Interleukin-17A inhibition diminishes inflammation and new bone formation in experimental spondyloarthritis","volume":"71","author":"van Tok","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"2025090312091176000_6.2.e001306.3","doi-asserted-by":"crossref","unstructured":"Braun J , Baraliakos X , Deodhar A , et al. 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