Correlation of protease-activated receptor-2 expression and synovitis in rheumatoid and osteoarthritis
dc.contributor.author | Walsh, David A | |
dc.date.accessioned | 2022-04-25T13:06:27Z | |
dc.date.available | 2022-04-25T13:06:27Z | |
dc.date.issued | 2012-10 | |
dc.identifier.citation | Tindell, AG, Kelso, EB, Ferrell, WR, Lockhart, JC, Walsh, DA, Dunning, L & McInnes, IB 2012, ‘Correlation of protease-activated receptor-2 expression and synovitis in rheumatoid and osteoarthritis’, RHEUMATOLOGY INTERNATIONAL -BERLIN-, vol. 32, no. 10, pp. 3077–3086 | en_US |
dc.identifier.uri | http://hdl.handle.net/20.500.12904/15370 | |
dc.description.abstract | Protease-activated receptor-2 (PAR-2) is known to be pro-inflammatory and increasing evidence points to an inflammatory component in osteoarthritis. This investigation examined the relationship between synovitis and PAR-2 expression, histological and immunohistochemical analysis being performed on synovial samples obtained from OA and RA patients, along with non-arthritic samples obtained by post mortem (PM). Samples were also analysed for PAR-4 expression, this receptor also having putative pro-inflammatory roles. Analysis involved comparison of inflammatory indices (synovial thickness and monocyte infiltration) with expression of PAR-2 and PAR-4. Synovial explants were also analysed for TNFα generation in the presence of a PAR-2 antagonist (ENMD-1068) or vehicle. OA synovia showed heterogeneity of inflammatory indicators, some samples overlapping with those from the RA cohort whilst others appeared similar to the PM cohort. PAR-2 expression, both in the lining layer and the interstitium, correlated strongly and significantly with synovial thickness (r = 0.91) and monocyte infiltration (r = 0.83), respectively (P < 0.001 in both cases), and this remains significant on individual cohort analysis. PAR-2 was co-localised to CD3 and CD68 cells in RA and OA synovium as well as fibroblasts derived from these synovia. PAR-4 was also expressed, but the relationship with inflammatory indicators was substantially weaker. Inflammatory indicators in OA synovia showed considerable variability, but correlated strongly with PAR-2 expression, suggesting PAR-2 upregulation in synovitis. Heterogeneity of inflammatory indicators was paralleled by wide variation in TNFα generation between samples. Secretion of this cytokine was dose-dependently inhibited by ENMD-1068, providing evidence of a functional role for PAR-2 in promoting synovitis. | |
dc.description.uri | https://link.springer.com/article/10.1007/s00296-011-2102-9 | en_US |
dc.publisher | Rheumatology International | en_US |
dc.subject | Synovitis | en_US |
dc.subject | Osteoarthritis | en_US |
dc.title | Correlation of protease-activated receptor-2 expression and synovitis in rheumatoid and osteoarthritis | en_US |
dc.type | Article | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
rioxxterms.version | NA | en_US |
rioxxterms.versionofrecord | 10.1007/s00296-011-2102-9. | en_US |
rioxxterms.type | Journal Article/Review | en_US |
refterms.panel | Unspecified | en_US |
refterms.dateFirstOnline | 2011-09 | |
html.description.abstract | Protease-activated receptor-2 (PAR-2) is known to be pro-inflammatory and increasing evidence points to an inflammatory component in osteoarthritis. This investigation examined the relationship between synovitis and PAR-2 expression, histological and immunohistochemical analysis being performed on synovial samples obtained from OA and RA patients, along with non-arthritic samples obtained by post mortem (PM). Samples were also analysed for PAR-4 expression, this receptor also having putative pro-inflammatory roles. Analysis involved comparison of inflammatory indices (synovial thickness and monocyte infiltration) with expression of PAR-2 and PAR-4. Synovial explants were also analysed for TNFα generation in the presence of a PAR-2 antagonist (ENMD-1068) or vehicle. OA synovia showed heterogeneity of inflammatory indicators, some samples overlapping with those from the RA cohort whilst others appeared similar to the PM cohort. PAR-2 expression, both in the lining layer and the interstitium, correlated strongly and significantly with synovial thickness (r = 0.91) and monocyte infiltration (r = 0.83), respectively (P < 0.001 in both cases), and this remains significant on individual cohort analysis. PAR-2 was co-localised to CD3 and CD68 cells in RA and OA synovium as well as fibroblasts derived from these synovia. PAR-4 was also expressed, but the relationship with inflammatory indicators was substantially weaker. Inflammatory indicators in OA synovia showed considerable variability, but correlated strongly with PAR-2 expression, suggesting PAR-2 upregulation in synovitis. Heterogeneity of inflammatory indicators was paralleled by wide variation in TNFα generation between samples. Secretion of this cytokine was dose-dependently inhibited by ENMD-1068, providing evidence of a functional role for PAR-2 in promoting synovitis. | en_US |
rioxxterms.funder.project | 94a427429a5bcfef7dd04c33360d80cd | en_US |