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dc.contributor.authorJones, Rebecca C
dc.contributor.authorLawrence, Kevin M
dc.contributor.authorHiggins, Scott M
dc.contributor.authorRichardson, S M
dc.contributor.authorTownsend, Paul A
dc.date.accessioned2022-06-22T07:18:29Z
dc.date.available2022-06-22T07:18:29Z
dc.date.issued2022en
dc.identifier.citationJones RC, Lawrence KM, Higgins SM, Richardson SM, Townsend PA. Urocortin-1 Is Chondroprotective in Response to Acute Cartilage Injury via Modulation of Piezo1. Vol. 23, International Journal of Molecular Sciences. MDPI AG; 2022. p. 5119.en
dc.identifier.pmid35563508en
dc.identifier.doi10.3390/ijms23095119en
dc.identifier.urihttp://hdl.handle.net/10541/625306
dc.description.abstractPost-traumatic OA (PTOA) is often triggered by injurious, high-impact loading events which result in rapid, excessive chondrocyte cell death and a phenotypic shift in residual cells toward a more catabolic state. As such, the identification of a disease-modifying OA drug (DMOAD) that can protect chondrocytes from death following impact injury, and thereby prevent cartilage degradation and progression to PTOA, would offer a novel intervention. We have previously shown that urocortin-1 (Ucn) is an essential endogenous pro-survival factor that protects chondrocytes from OA-associated pro-apoptotic stimuli. Here, using a drop tower PTOA-induction model, we demonstrate the extent of Ucn's chondroprotective role in cartilage explants exposed to excessive impact load. Using pathway-specific agonists and antagonists, we show that Ucn acts to block load-induced intracellular calcium accumulation through blockade of the non-selective cation channel Piezo1 rather than TRPV4. This protective effect is mediated primarily through the Ucn receptor CRF-R1 rather than CRF-R2. Crucially, we demonstrate that the chondroprotective effect of Ucn is maintained whether it is applied pre-impact or post-impact, highlighting the potential of Ucn as a novel DMOAD for the prevention of injurious impact overload-induced PTOA.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.3390/ijms23095119en
dc.titleUrocortin-1 is chondroprotective in response to acute cartilage injury via modulation of Piezo1en
dc.typeArticleen
dc.contributor.departmentManchester Cancer Research Centre, Division of Cancer Sciences, Faculty of Biology, School of Medical Sciences, Medicine and Health, University of Manchester, Wilmslow Road, Manchester M20 4GJ, UKen
dc.identifier.journalInternational Journal of Molecular Sciencesen
dc.description.noteen]
refterms.dateFOA2022-06-22T08:17:36Z


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