FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2950111625> ?p ?o ?g. }

• W2950111625 abstract "Osteoarthritis (OA) is the most common degenerative joint disease, and joint injury increases the risk of OA by 10-fold. Although the injury event itself damages joint tissues, a substantial amount of secondary damage is mediated by the cellular responses to the injury. Cellular responses include the production and activation of proteases (MMPs, ADAMTSs, Cathepsins), the production of inflammatory cytokines, and we hypothesize, changes to the joint metabolome. The trajectory of cellular responses is driven by the transcriptional activation of early response genes, which requires Cdk9-dependent RNA Polymerase II phosphorylation. Flavopiridol is a potent and selective inhibitor of Cdk9 kinase activity, which prevents the transcriptional activation of early response genes. To model post-traumatic osteoarthritis, we subjected mice to non-invasive ACL-rupture joint injury. Following injury, mice were treated with flavopiridol to inhibit Cdk9-dependent transcriptional activation, or vehicle control. Global joint metabolomics were analyzed 1 hour after injury. We found that injury induced metabolomic changes, including increases in Vitamin D3 metabolism and others. Importantly, we found that inhibition of primary response gene activation at the time of injury largely prevented the global changes in the metabolomics profiles. Cluster analysis of joint metabolomes identified groups of injury-induced and drug-responsive metabolites, which may offer novel targets for cell-mediated secondary joint damage. Metabolomic profiling provides an instantaneous snapshot of biochemical activity representing cellular responses, and these data demonstrate the potential for inhibition of early response genes to alter the trajectory of cell-mediated degenerative changes following joint injury. Significance Statement Joint injury is an excellent predictor of future osteoarthritis. It is increasingly apparent that the acute cellular responses to injury contribute to the initiation and pathogenesis of OA. Although changes to the joint transcriptome have been extensively studied in the context of joint injury, little is known about changes to small-molecule metabolites. Here we use a non-invasive ACL rupture model of joint injury in mice to identify injury-induced changes to the global metabolomic profiles. In one experimental group we prevented the activation of primary response gene transcription using the Cdk9 inhibitor flavopiridol. Through this comparison, we identified two sets of metabolites that change acutely after joint injury: those that require transcription of primary response genes, and those that do not." @default.
• W2950111625 created "2019-06-27" @default.
• W2950111625 creator A5021030176 @default.
• W2950111625 creator A5030543305 @default.
• W2950111625 creator A5032448354 @default.
• W2950111625 creator A5043312464 @default.
• W2950111625 creator A5066181773 @default.
• W2950111625 creator A5078441511 @default.
• W2950111625 date "2018-07-29" @default.
• W2950111625 modified "2023-09-26" @default.
• W2950111625 title "Inhibition of Early Response Genes Prevents Changes in Global Joint Metabolomic Profiles in Mouse Post-Traumatic Osteoarthritis" @default.
• W2950111625 cites W1839227508 @default.
• W2950111625 cites W1848620583 @default.
• W2950111625 cites W1905238978 @default.
• W2950111625 cites W1973401962 @default.
• W2950111625 cites W1973897421 @default.
• W2950111625 cites W1975328793 @default.
• W2950111625 cites W1982167517 @default.
• W2950111625 cites W1984277713 @default.
• W2950111625 cites W1985569332 @default.
• W2950111625 cites W1989299822 @default.
• W2950111625 cites W1989804575 @default.
• W2950111625 cites W1990453662 @default.
• W2950111625 cites W1990924615 @default.
• W2950111625 cites W1997062226 @default.
• W2950111625 cites W2005337876 @default.
• W2950111625 cites W2013381732 @default.
• W2950111625 cites W2018647053 @default.
• W2950111625 cites W2023493360 @default.
• W2950111625 cites W2024452130 @default.
• W2950111625 cites W2029732523 @default.
• W2950111625 cites W2030872525 @default.
• W2950111625 cites W2036698519 @default.
• W2950111625 cites W2043834774 @default.
• W2950111625 cites W2044633090 @default.
• W2950111625 cites W2051598492 @default.
• W2950111625 cites W2052646320 @default.
• W2950111625 cites W2053002159 @default.
• W2950111625 cites W2063028213 @default.
• W2950111625 cites W2064988047 @default.
• W2950111625 cites W2066107979 @default.
• W2950111625 cites W2078330227 @default.
• W2950111625 cites W2081465448 @default.
• W2950111625 cites W2088086541 @default.
• W2950111625 cites W2101197534 @default.
• W2950111625 cites W2109357220 @default.
• W2950111625 cites W2114676488 @default.
• W2950111625 cites W2116687544 @default.
• W2950111625 cites W2118963985 @default.
• W2950111625 cites W2124706850 @default.
• W2950111625 cites W2126711569 @default.
• W2950111625 cites W2130709982 @default.
• W2950111625 cites W2136478693 @default.
• W2950111625 cites W2145025818 @default.
• W2950111625 cites W2154142977 @default.
• W2950111625 cites W2164094541 @default.
• W2950111625 doi "https://doi.org/10.1101/379370" @default.
• W2950111625 hasPublicationYear "2018" @default.
• W2950111625 type Work @default.
• W2950111625 sameAs 2950111625 @default.
• W2950111625 citedByCount "0" @default.
• W2950111625 crossrefType "posted-content" @default.
• W2950111625 hasAuthorship W2950111625A5021030176 @default.
• W2950111625 hasAuthorship W2950111625A5030543305 @default.
• W2950111625 hasAuthorship W2950111625A5032448354 @default.
• W2950111625 hasAuthorship W2950111625A5043312464 @default.
• W2950111625 hasAuthorship W2950111625A5066181773 @default.
• W2950111625 hasAuthorship W2950111625A5078441511 @default.
• W2950111625 hasBestOaLocation W29501116251 @default.
• W2950111625 hasConcept C104317684 @default.
• W2950111625 hasConcept C142724271 @default.
• W2950111625 hasConcept C150194340 @default.
• W2950111625 hasConcept C162317418 @default.
• W2950111625 hasConcept C184235292 @default.
• W2950111625 hasConcept C204787440 @default.
• W2950111625 hasConcept C21565614 @default.
• W2950111625 hasConcept C2776164576 @default.
• W2950111625 hasConcept C55493867 @default.
• W2950111625 hasConcept C60644358 @default.
• W2950111625 hasConcept C71924100 @default.
• W2950111625 hasConcept C86803240 @default.
• W2950111625 hasConcept C95444343 @default.
• W2950111625 hasConceptScore W2950111625C104317684 @default.
• W2950111625 hasConceptScore W2950111625C142724271 @default.
• W2950111625 hasConceptScore W2950111625C150194340 @default.
• W2950111625 hasConceptScore W2950111625C162317418 @default.
• W2950111625 hasConceptScore W2950111625C184235292 @default.
• W2950111625 hasConceptScore W2950111625C204787440 @default.
• W2950111625 hasConceptScore W2950111625C21565614 @default.
• W2950111625 hasConceptScore W2950111625C2776164576 @default.
• W2950111625 hasConceptScore W2950111625C55493867 @default.
• W2950111625 hasConceptScore W2950111625C60644358 @default.
• W2950111625 hasConceptScore W2950111625C71924100 @default.
• W2950111625 hasConceptScore W2950111625C86803240 @default.
• W2950111625 hasConceptScore W2950111625C95444343 @default.
• W2950111625 hasLocation W29501116251 @default.
• W2950111625 hasLocation W29501116252 @default.
• W2950111625 hasLocation W29501116253 @default.
• W2950111625 hasOpenAccess W2950111625 @default.
• W2950111625 hasPrimaryLocation W29501116251 @default.

• next