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 | MIT 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.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. Department of Biological Engineering | |
dc.identifier.oclc | 156949527 | en_US |