Millar, N. L. , Gilchrist, D. S., Kurowska-Stolarska, M. , Murrell, G. A.C. and McInnes, I. (2013) The Interleukin 33/miR29 Axis Regulates Differential Collagen Production in Tendinopathy. In: 77th Annual Meeting of the American College of Rheumatology / 48th Annual Meeting of the Association of Rheumatology Health Professionals, San Diego, CA, 26-30 Oct 2013., S405.
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Abstract
Background/Purpose: Tendon disorders comprise the commonest musculoskeletal clinical presentation and accordingly represent a significant unmet clinical need in rheumatology. Recent animal and human studies have highlighted a central role for inflammation and subsequent matrix remodeling in tendon pathophysiology. Interleukin-33 (IL-33) acting via its receptor ST2 is increasingly recognized as a critical endogenous tissue danger signal that can initiate inflammation. We investigated the role of the IL-33/ST2 signaling pathway on tendon pathology in animal and human models of tendinopathy. <br>Methods: Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon ACL reconstruction. The impact of microRNA 29 upon tenocyte biology ex vivo was measured using quantitative RT-PCR, collagen I/III ELISAs and luminex cytokine multiplexes.</br> <br> 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 neutralizing 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. In particular we show that miR29a selectively targets Collagen III through distal polyadenylation sites.</br> Conclusion: 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.
| Item Type: | Conference Proceedings |
|---|---|
| Additional Information: | <br>Special Issue: 2013 Annual Meeting Abstract Supplement</br> Arthritis and Rheumatism 65(10):S405 |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Gilchrist, Dr Derek and Millar, Professor Neal and Kurowska-Stolarska, Professor Mariola |
| Authors: | Millar, N. L., Gilchrist, D. S., Kurowska-Stolarska, M., Murrell, G. A.C., and McInnes, I. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Arthritis and Rheumatism |
| Publisher: | Wiley-Blackwell |
| ISSN: | 0004-3591 |
| ISSN (Online): | 1529-0131 |
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