PT - JOURNAL ARTICLE AU - Mittal Shah AU - Asher Maroof AU - Panos Gikas AU - Gayatri Mittal AU - Richard Keen AU - Dominique Baeten AU - Stevan Shaw AU - Scott J Roberts TI - Dual neutralisation of IL-17F and IL-17A with bimekizumab blocks inflammation-driven osteogenic differentiation of human periosteal cells AID - 10.1136/rmdopen-2020-001306 DP - 2020 Jul 01 TA - RMD Open PG - e001306 VI - 6 IP - 2 4099 - http://rmdopen.bmj.com/content/6/2/e001306.short 4100 - http://rmdopen.bmj.com/content/6/2/e001306.full SO - RMD Open2020 Jul 01; 6 AB - Objectives 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.Methods 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.Results Recombinant IL-17A and IL-17F are pro-osteogenic with respect to hPDC differentiation. T helper 17 or γδ-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 DKK1. 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.Conclusions 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.