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.
- Ankylosing Spondylitis
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Contributors MS, SR, RK and SS contributed to the conception and design of the study. MS and AM were involved in the acquisition of data. PG, GM and RK provided scientific/clinical interpretation and patient material/data acquisition. MS, AM, DB, SS and SR contributed to the analysis and interpretation of data. SR supervised the study. All authors contributed to drafting and/or revising the manuscript.
Funding This work was funded by UCB Pharma.
Competing interests MS, AM, SS and DB are employees of UCB Pharma. PG has received honoraria from Medacta International. RK has received honoraria from Kyowa Kirin, Amgen and Clementia Pharmaceuticals, and consulting fees from Kyowa Kirin and Clementia Pharmaceuticals. SR is a former employee of UCB Pharma and has received consulting fees from Angitia Biopharmaceuticals.
Patient consent for publication Not required.
Ethics approval This study was approved by the NHS Research Ethics Committee (research authority: Yorkshire and the Humber—Leeds West Research Ethics Committee 16/YH/0137).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
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