| http://purl.uniprot.org/citations/30518918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30518918 | http://www.w3.org/2000/01/rdf-schema#comment | "Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. In OA, chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favouring disease progression. Similar to other wound-healing disorders, chondrocytes from OA patients show a chronic increase in the gap junction channel protein connexin43 (Cx43), which regulates signal transduction through the exchange of elements or recruitment/release of signalling factors. Although immature or stem-like cells are present in cartilage from OA patients, their origin and role in disease progression are unknown. In this study, we found that Cx43 acts as a positive regulator of chondrocyte-mesenchymal transition. Overactive Cx43 largely maintains the immature phenotype by increasing nuclear translocation of Twist-1 and tissue remodelling and proinflammatory agents, such as MMPs and IL-1β, which in turn cause cellular senescence through upregulation of p53, p16INK4a and NF-κB, contributing to the senescence-associated secretory phenotype (SASP). Downregulation of either Cx43 by CRISPR/Cas9 or Cx43-mediated gap junctional intercellular communication (GJIC) by carbenoxolone treatment triggered rediferentiation of osteoarthritic chondrocytes into a more differentiated state, associated with decreased synthesis of MMPs and proinflammatory factors, and reduced senescence. We have identified causal Cx43-sensitive circuit in chondrocytes that regulates dedifferentiation, redifferentiation and senescence. We propose that chondrocytes undergo chondrocyte-mesenchymal transition where increased Cx43-mediated GJIC during OA facilitates Twist-1 nuclear translocation as a novel mechanism involved in OA progression. These findings support the use of Cx43 as an appropriate therapeutic target to halt OA progression and to promote cartilage regeneration."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41419-018-1225-2"xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Aasen T."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Blanco A."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Fonseca E."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Largo R."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Tabernero A."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Kandouz M."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Mayan M.D."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Caeiro J.R."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Varela-Eirin M."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Varela-Vazquez A."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Guitian-Caamano A."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Mato V."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/author | "Paino C.L."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/name | "Cell Death Dis"xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/pages | "1166"xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/title | "Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis."xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://purl.uniprot.org/core/volume | "9"xsd:string |
| http://purl.uniprot.org/citations/30518918 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30518918 |
| http://purl.uniprot.org/citations/30518918 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30518918 |
| http://purl.uniprot.org/uniprot/#_Q15672-mappedCitation-30518918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30518918 |
| http://purl.uniprot.org/uniprot/#_A0A654IBU3-mappedCitation-30518918 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30518918 |