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Cartilage mechanobiology and transcriptional effects of combined mechanical compression and IGF-1 stimulation on bovine cartilage explants

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dc.contributor.advisor Alan J. Grodzinsky. en_US
dc.contributor.author Wheeler, Cameron, 1978- en_US
dc.contributor.other Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.date.accessioned 2007-08-29T20:35:12Z
dc.date.available 2007-08-29T20:35:12Z
dc.date.copyright 2006 en_US
dc.date.issued 2007 en_US
dc.identifier.uri http://hdl.handle.net/1721.1/38613
dc.description Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, February 2007. en_US
dc.description Includes bibliographical references. en_US
dc.description.abstract Background: 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.statementofresponsibility by Cameron A. Wheeler. en_US
dc.format.extent 77, 1509-1517 leaves en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri http://dspace.mit.edu/handle/1721.1/7582
dc.subject Biological Engineering Division. en_US
dc.title Cartilage mechanobiology and transcriptional effects of combined mechanical compression and IGF-1 stimulation on bovine cartilage explants en_US
dc.type Thesis en_US
dc.description.degree S.M. en_US
dc.contributor.department Massachusetts Institute of Technology. Biological Engineering Division. en_US
dc.identifier.oclc 156949527 en_US


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