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OP0259 The Interleukin 33/MIR29 Axis Regulates Differential Collagen Production in Tendinopathy
  1. N. L. Millar1,
  2. D. S. Gilchrist1,
  3. M. Kurowska-Stolarska1,
  4. G. A. C. Murrell2,
  5. I. B. McInnes1
  1. 1Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
  2. 2Orthopaedic Research Institute, University of New South Wales, Sydney, Australia

Abstract

Background Tendon disorders comprise the commonest musculoskeletal clinical presentation and accordingly represent a significant unmet clinical need. Recent animal and human studies have highlighted a central role for inflammation and subsequent matrix remodelling in tendon pathophysiology. Interleukin-33 (IL-33) acting via its receptor ST2 is increasingly recognised as a critical endogenous tissue danger signal that can initiate inflammation.

Objectives We investigated the role of the IL-33/ST2 signallingpathway on tendon pathology in animal and human models of tendinopathy.

Results We show here that human and mouse tendons over express IL-33 when damaged, and drives tenocytes to undergo an early switch in collagen matrix production toward a collagen III phenotype. Moreover, administration of rh IL-33 in an in vivo model of tendinopathy results in reduced biomechanical tendon strength at early time points while neutralising antibodies to IL-33 attenuates these changes. Furthermore we highlight a key regulatory role for the microRNA29 family in IL-33 induced collagen matrix changes through direct targeting of the soluble ST2 receptor and Collagen III.

Conclusions For the first time we provide evidence that IL-33/miR-29 pathway orchestrates inflammatory and matrix responses following tissue injury, and thus may offer future strategies to treat tendon diseases diseases.

Disclosure of Interest None Declared

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