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dc.contributor.authorTimmer, Tysen
dc.contributor.authorJune, Ron
dc.date.accessioned2017-09-14T09:00:23Z
dc.date.available2017-09-14T09:00:23Z
dc.date.issued2016-01-30
dc.identifier.urihttp://hdl.handle.net/1773/40342
dc.description.abstractBackground- The menisci act as one of the main stabilizing and load distributing structures in the knee joint. They are composed mostly of structured type 1 collagen, proteoglycans, and meniscal fibrochondrocytes and are the most commonly injured structure of the knee. The tissue is only capable of limited self repair in the case of injury. One exciting new area of research is using metabolomics to study mechanotransduction. This technique quantitatively profiles the processes by which cells respond to mechanical stimuli by biochemical signals that characterize downstream cellular responses. Objective- The objective was to identify candidate mediators of meniscal fibrochondrocyte mechanotransduction in mouse tissues using in vitro organ culture. We aim to uncover metabolomic differences between injured and uninjured tissues and also differences between the tissues in isolation and in combination. Methods- Mouse knee tissue samples were randomly assigned to isolated or combination experimental groups. The structures were cultured for 12 days with half of the menisci being injured. Metabolites were characterized by HPLCMS and untargeted metabolomic analysis to examine changes in global metabolomic profiles. Results- Untargeted metabolomics and cluster analysis revealed changes in 1440 total metabolites, as well as changes in regulation of metabolomic pathways in the response of isolated menisci to injury compared to uninjured isolated menisci. For tissues cultured in combination, similar results were obtained with activation of a larger number of pathways. We discovered a total of 111 metabolic pathways altered by injury. Frequency analysis of individual metabolites in one of the combination samples revealed that the top ten individual metabolites are present in a majority of the upregulated pathways. Conclusions- These data show that metabolomic differences exist between injured and uninjured meniscal fibrochondrocytes, and also metabolomic differences exist when comparing the response of these injured isolated samples to that of injured samples in combination with other knee tissues.en_US
dc.description.sponsorshipUniversity of Washington School of Medicine Montana State Universityen_US
dc.language.isoen_USen_US
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectMetabolomicen_US
dc.subjectprofilingen_US
dc.subjectMetabolomic profilingen_US
dc.subjectmeniscal tearsen_US
dc.subjectmeniscal tearen_US
dc.subjectcartilageen_US
dc.subjectmetabolicen_US
dc.subjectinjuryen_US
dc.subjectfibrocartilageen_US
dc.subjectmeniscusen_US
dc.subjectMenisectomyen_US
dc.subjectOCDen_US
dc.subjectlesionen_US
dc.subjectsynoviumen_US
dc.subjectsynovialen_US
dc.subjecttendonen_US
dc.subjectligamenten_US
dc.subjectKneeen_US
dc.subjectcapsuleen_US
dc.titleMetabolomic Profiling of a Novel In Vitro Model of Meniscal Tearsen_US
dc.typeWorking Paperen_US


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CC0 1.0 Universal
Except where otherwise noted, this item's license is described as CC0 1.0 Universal