Stromal ‘activation’ markers do not confer pathogenic activity in tendinopathy

Crowe, L. A.N., Melchor, E. G., Murrell, G. A.C., McInnes, I. B. , Akbar, M. and Millar, N. (2021) Stromal ‘activation’ markers do not confer pathogenic activity in tendinopathy. Translational Sports Medicine, 4(2), pp. 268-279. (doi: 10.1002/tsm2.204)

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Abstract

Tendinopathy is a highly prevalent musculoskeletal pathology associated with incremental injury as result of repetitive microtrauma. We sought to explore the physiological significance of stromal “activation” signatures in a human model of tendinopathy. Torn supraspinatus tendon and matched intact subscapularis tendon biopsies were collected from patients undergoing shoulder surgery while healthy tendon was collected from patients undergoing anterior cruciate ligament (ACL) reconstruction. Expression of stromal activation markers was analyzed at transcript/protein level using qRT‐PCR and immunohistochemistry. Gene expression of stromal activation markers was silenced by siRNA‐mediated knockdown or induced by IL‐1β stimulation. Expression of “activation” markers podoplanin, VCAM‐1 and CD248 was identified in human tendon tissue. Podoplanin and VCAM‐1 expression were significantly increased in tendinopathic tissue. Knockdown of podoplanin and VCAM‐1 in normal and tendinopathic tenocytes did not have any significant effect on expression of matrix genes COL1A1, COL3A1, TNC, or DCN. Similarly, no changes in release of inflammatory mediators IL‐6, IL‐8, and CCL2 were observed in podoplanin/VCAM‐1 knockdown cultures. Our data suggest that silencing expression of stromal “activation” markers does not affect the intrinsic inflammatory profile or matrix regulatory behavior of tenocytes. We propose that the term “activation” is more appropriately reflected by alterations in tenocyte behavior that induce changes in the stromal microenvironment and overall tissue architecture rather than identification through potentially arbitrary phenotypic traits.

Item Type:Articles
Additional Information:This work was funded by the Medical Research Council (MR/R020515/1).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Akbar, Mr Moeed and Crowe, Ms Lindsay and Millar, Professor Neal
Authors: Crowe, L. A.N., Melchor, E. G., Murrell, G. A.C., McInnes, I. B., Akbar, M., and Millar, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Translational Sports Medicine
Publisher:Wiley
ISSN:2573-8488
ISSN (Online):2573-8488
Published Online:30 September 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Translational Sports Medicine 4(2):268-279
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301515Damage mechanisms in tendon diseaseNeal MillarMedical Research Council (MRC)MR/R020515/1III - Immunology