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dc.contributor.advisorAlan J. Grodzinsky.en_US
dc.contributor.authorWheeler, Cameron, 1978-en_US
dc.contributor.otherMassachusetts Institute of Technology. Biological Engineering Division.en_US
dc.date.accessioned2007-08-29T20:35:12Z
dc.date.available2007-08-29T20:35:12Z
dc.date.copyright2006en_US
dc.date.issued2007en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/38613
dc.descriptionThesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, February 2007.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractBackground: Investigators have focused on mechano-regulation of upstream signaling and responses at the level of gene transcription, protein translation and post-translational modifications. Intracellular pathways including those involving integrin signaling, mitogen activated protein kinases (MAPKs), and release of intracellular calcium have been confirmed in several laboratories. Studies with IGF-1: Insulin-like growth factor-I (IGF-1) is a potent anabolic factor capable of endocrine and paracrine/autocrine signaling. Previous studies have demonstrated that mechanical compression can regulate the action of IGF-1 on chondrocyte biosynthesis in intact tissue; when applied simultaneously, these stimuli act by distinct cell activation pathways. Our objectives were to elucidate the extent and kinetics of the chondrocyte transcriptional response to combined IGF-1 and static compression in cartilage explants. Discussion: Clustering analysis revealed five distinct groups. TIMP-3 and ADAMTS-5, MMP-l and IGF-2, and IGF-1 and Collagen II, were all robustly co-expressed under all conditions tested. In comparing gene expression levels to previously measured aggrecan biosynthesis levels, aggrecan synthesis is shown to be transcriptionally regulated by IGF- 1, whereas inhibition of aggrecan synthesis by compression is not transcriptionally regulated.en_US
dc.description.abstract(cont.) Conclusion: Many genes measured are responsive the effects of IGF-1 under 0% compression and 50% compression. Clustering analysis revealed strong co-expressed gene pairings. IGF-1 stimulates aggrecan biosynthesis in a transcriptionally regulated manner, whereas compression inhibits aggrecan synthesis in a manner not regulated by transcriptional activity.en_US
dc.description.statementofresponsibilityby Cameron A. Wheeler.en_US
dc.format.extent77, 1509-1517 leavesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582
dc.subjectBiological Engineering Division.en_US
dc.titleCartilage mechanobiology and transcriptional effects of combined mechanical compression and IGF-1 stimulation on bovine cartilage explantsen_US
dc.typeThesisen_US
dc.description.degreeS.M.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineering
dc.identifier.oclc156949527en_US


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