A ROLE FOR IL-17A IN THE SUPPRESSION OF SPINAL ENTHESEAL MESENCHYMAL STEM CELL ADIPOGENESIS WHILST SIMULTANEOUSLY FACILITATING OSTEOGENESIS.

Background: Fat formation in the bone adjacent to the enthesis is an important but poorly characterised intermediate stage in new bone formation that occurs in the spine in AS. We and others have previously reported that IL-17A can increase mesenchymal stem cell (MSC) mediated osteogenesis in normal and AS spinal tissue (1, 2). Objectives: Herein we investigate the impact of IL-17A \u0026 TNF on MSC adipogenesis from spinal enthesis tissue. Methods: Samples from healthy spinous process and interspinous ligament (n=14, median age = 53) were separated into the peri-entheseal bone (PEB) and entheseal soft tissue (EST) \u0026 enzymatically digested. Minimally passaged ( Results: EST MSCs have a significantly higher adipogenic potential than matched PEB MSCs (n=14, p Conclusion: Given the inverse link between MSC mediated osteogeneis \u0026 adipogenesis, these findings reveal a role of IL-17A especially on EST MSCs. The rapid formation of adipocytes seen in EST MSCs may be relevant to MRI determined peri-entheseal bone “shiny corners” due to post inflammation fat accumulation. Elevated transcripts associated with pre-adipocytes \u0026 undifferentiated MSCs support the idea of plasticity between early osteogenesis \u0026 adipogenesis. Downregulation of transcripts for proteins associated with protection against lipolysis allows for the rationalising of the gradual loss of the shiny corners seen in AS preceding subsequent new bone formation. References: [1]RUSSELL, T., A. WATAD, C. BRIDGEWOOD, A. KHAN, A.S. RAO, P. LOUGHENBURY, P. MILNER, R. DUNSMUIR, T. BABOOLAL, E. JONES, R. CUTHBERT and D. MCGONAGLE. IL-17A Induces Distinct Functional Differences Between Two Novel Mesenchymal Stem Cell Populations Identified at the Human Enthesis. Arthritis Rheumatol, 2019, 71 Suppl 10, pp.1-5362. [2]JO, S., S.E. WANG, Y.L. LEE, S. KANG, B. LEE, J. HAN, I.H. SUNG, Y.S. PARK, S.C. BAE and T.H. KIM. IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis. Arthritis Res Ther, 2018, 20(1), p.115. [3]AHMED, M. and S.L. GAFFEN. IL-17 in obesity and adipogenesis. Cytokine Growth Factor Rev, 2010, 21(6), pp.449-53. [4]HANSEN, J.S., S. DE MARE, H.A. JONES, O. GORANSSON and K. LINDKVIST-PETERSSON. Visualization of lipid directed dynamics of perilipin 1 in human primary adipocytes. Sci Rep, 2017, 7(1), p.15011. Disclosure of Interests: Tobias Russell Grant/research support from: Novartis UK Investigator Initiated non-clinical research funding support, Charlie Bridgewood: None declared, Almas Khan: None declared, Abhay S Rao: None declared, Peter Loughenbury: None declared, Peter Millner: None declared, Robert Dunsmuir: None declared, Ala Altaie: None declared, Elena Jones: None declared, Dennis McGonagle Grant/research support from: Janssen Research \u0026 Development, LLC