McCulloch, K., McGrath, S., Huesa, C., Dunning, L., Litherland, G., Crilly, A., Hultin, L., Ferrell, W. R., Lockhart, J. C. and Goodyear, C. S. (2018) Rheumatic disease: protease-activated receptor-2 in synovial joint pathobiology. Frontiers in Endocrinology, 9, 257. (doi: 10.3389/fendo.2018.00257) (PMID:29875735) (PMCID:PMC5974038)
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Abstract
Protease-activated receptor-2 (PAR2) is one member of a small family of transmembrane, G-protein-coupled receptors. These receptors are activated via cleavage of their N terminus by serine proteases (e.g., tryptase), unveiling an N terminus tethered ligand which binds to the second extracellular loop of the receptor. Increasing evidence has emerged identifying key pathophysiological roles for PAR2 in both rheumatoid arthritis (RA) and osteoarthritis (OA). Importantly, this includes both pro-inflammatory and destructive roles. For example, in murine models of RA, the associated synovitis, cartilage degradation, and subsequent bone erosion are all significantly reduced in the absence of PAR2. Similarly, in experimental models of OA, PAR2 disruption confers protection against cartilage degradation, subchondral bone osteosclerosis, and osteophyte formation. This review focuses on the role of PAR2 in rheumatic disease and its potential as an important therapeutic target for treating pain and joint degradation.
| Item Type: | Articles |
|---|---|
| Additional Information: | ** From Europe PMC via Jisc Publications Router. ** Licence for this article: cc by |
| Keywords: | Cartilage, Rheumatoid arthritis, Bone, Osteoarthritis, Synovium, Protease-activated Receptor-2 |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Huesa, Dr Carmen |
| Authors: | McCulloch, K., McGrath, S., Huesa, C., Dunning, L., Litherland, G., Crilly, A., Hultin, L., Ferrell, W. R., Lockhart, J. C., and Goodyear, C. S. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Frontiers in Endocrinology |
| Publisher: | Frontiers Research Foundation |
| ISSN: | 1664-2392 |
| ISSN (Online): | 1664-2392 |
| Copyright Holders: | Copyright © 2018 McCulloch, McGrath, Huesa, Dunning, Litherland, Crilly, Hultin, Ferrell, Lockhart and Goodyear |
| First Published: | First published in Frontiers in Endocrinology 9:257 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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