Ferrell, W.R., Kelso, E.B., Lockhart, J.C., Plevin, R. and McInnes, I.B. (2010) Protease-activated receptor 2: a novel pathogenic pathway in a murine model of osteoarthritis. Annals of the Rheumatic Diseases, 69(11), pp. 2051-2054. (doi: 10.1136/ard.2010.130336) (PMID:20584806)
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Publisher's URL: http://dx.doi.org/10.1136/ard.2010.130336
Abstract
<b>Objective:</b> Osteoarthritis is a global clinical challenge for which no effective disease-modifying agents currently exist. This study identified protease-activated receptor 2 (PAR-2) as a novel pathogenic mechanism and potential therapeutic target in osteoarthritis. <br></br> <b>Methods:</b> Experimental osteoarthritis was induced in wild-type and PAR-2-deficient mice by sectioning the medial meniscotibial ligament (MMTL), leading to the development of a mild arthropathy. Cartilage degradation and increased subchondral bone formation were assessed as indicators of osteoarthritis pathology. <br></br> <b>Results:</b> Four weeks following MMTL section, cartilage erosion and increased subchondral bone formation was evident in wild-type mice but was substantially reduced in PAR-2-deficient mice. Crucially, the therapeutic inhibition of PAR-2 in wild-type mice, using either a PAR-2 antagonist or a monoclonal antibody targeting the protease cleavage site of PAR-2, was also equally effective at reducing osteoarthritis progression in vivo. PAR-2 was upregulated in chondrocytes of wild-type but not sham-operated mice. Wild-type mice showed further joint degradation 8 weeks after the induction of osteoarthritis, but PAR-2-deficient mice were still protected. <br></br> <b>Conclusions:</b> The substantial protection from pathology afforded by PAR-2 deficiency following the induction of osteoarthritis provides proof of concept that PAR-2 plays a key role in osteoarthritis and suggests this receptor as a potential therapeutic target.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Ferrell, Professor William |
Authors: | Ferrell, W.R., Kelso, E.B., Lockhart, J.C., Plevin, R., and McInnes, I.B. |
Subjects: | Q Science > QR Microbiology > QR180 Immunology |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Annals of the Rheumatic Diseases |
Publisher: | B M J Group |
ISSN: | 0003-4967 |
ISSN (Online): | 1468-2060 |
Published Online: | 01 January 2010 |
Copyright Holders: | Copyright © 2010 BMJ |
First Published: | First published in Annals of the Rheumatic Diseases |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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