Urocortin-1 is chondroprotective in response to acute cartilage injury via modulation of Piezo1
dc.contributor.author | Jones, Rebecca C | |
dc.contributor.author | Lawrence, Kevin M | |
dc.contributor.author | Higgins, Scott M | |
dc.contributor.author | Richardson, S M | |
dc.contributor.author | Townsend, Paul A | |
dc.date.accessioned | 2022-06-22T07:18:29Z | |
dc.date.available | 2022-06-22T07:18:29Z | |
dc.date.issued | 2022 | en |
dc.identifier.citation | Jones 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.pmid | 35563508 | en |
dc.identifier.doi | 10.3390/ijms23095119 | en |
dc.identifier.uri | http://hdl.handle.net/10541/625306 | |
dc.description.abstract | Post-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.iso | en | en |
dc.relation.url | https://dx.doi.org/10.3390/ijms23095119 | en |
dc.title | Urocortin-1 is chondroprotective in response to acute cartilage injury via modulation of Piezo1 | en |
dc.type | Article | en |
dc.contributor.department | Manchester 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, UK | en |
dc.identifier.journal | International Journal of Molecular Sciences | en |
dc.description.note | en] | |
refterms.dateFOA | 2022-06-22T08:17:36Z |