dc.contributor.advisor | Ray, Bimal K. | eng |
dc.contributor.author | Dhar, Srijita | eng |
dc.date.issued | 2009 | eng |
dc.date.submitted | 2009 Fall | eng |
dc.description | The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. | eng |
dc.description | Title from PDF of title page (University of Missouri--Columbia, viewed on March 3, 2011). | eng |
dc.description | Vita. | eng |
dc.description | Thesis advisor: Bimal K. Ray. | eng |
dc.description | M.S. University of Missouri-Columbia 2009. | eng |
dc.description.abstract | [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] ADAM 12 overexpression is linked to the pathology of diseases including osteoarthritis, cancer, cardiac hypertrophy, Alzheimers and multiple sclerosis. Degradation of fibrous cap and neo chondrogenesis are key events of OA. Several growth promoting agents including transforming growth factor-[beta] (TGF-[beta]) also play determining roles in the function of the cartilage specific cells. The potential link between growth factors and the pathogenesis of OA still remains unresolved. In the present study, we investigated TGF-[beta] mediated transcriptional induction of ADAM 12 in osteoblasts and synoviocytes, two of the resident cells of the joint. CAT assay revealed both positive and negative functioning elements at the proximal and the first exonic region of human ADAM 12 promoter. By using EMSA we showed increased interaction of NF[kappa]B, SAF-1 and Sp1 with the ADAM 12 promoter in TGF-[beta] stimulated cells. At the exonic region we also identified a highly conserved polydinucleotide repeat sequence that acts as a potent basal transcriptional repressor. These results suggest that the cohort action of NF[kappa]B, Sp1 and SAF-1 lead to the overexpression of ADAM 12 under osteoarthritic conditions. | eng |
dc.description.bibref | Includes bibliographical references. | eng |
dc.format.extent | viii, 92 pages | eng |
dc.identifier.oclc | 705358705 | eng |
dc.identifier.uri | https://doi.org/10.32469/10355/10290 | eng |
dc.identifier.uri | https://hdl.handle.net/10355/10290 | |
dc.language | English | eng |
dc.publisher | University of Missouri--Columbia | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Graduate School. Theses and Dissertations | eng |
dc.rights | Access is limited to the campuses of the University of Missouri. | eng |
dc.subject.lcsh | Membrane proteins -- Physiological transport | eng |
dc.subject.lcsh | Osteoarthritis -- Pathogenesis | eng |
dc.subject.lcsh | Articular cartilage -- Metabolism | eng |
dc.subject.lcsh | NF-kappa B (DNA-binding protein) -- Metabolism | eng |
dc.subject.lcsh | Transforming growth factors-beta -- Metabolism | eng |
dc.subject.lcsh | Bone cells -- Metabolism | eng |
dc.subject.lcsh | Synovial membranes -- Metabolism | eng |
dc.subject.lcsh | Metalloproteinases -- Metabolism | eng |
dc.subject.mesh | ADAM Proteins -- metabolism | eng |
dc.subject.mesh | Cartilage, Articular -- metabolism | eng |
dc.subject.mesh | Osteoarthritis -- pathology | eng |
dc.subject.mesh | Transforming Growth Factor beta -- pharmacology | eng |
dc.subject.mesh | NF-kappa B -- metabolism | eng |
dc.subject.mesh | Sp1 Transcription Factor -- metabolism | eng |
dc.subject.mesh | Osteoblasts -- metabolism | eng |
dc.subject.mesh | Synovial Membrane -- metabolism | eng |
dc.title | Transcriptional regulation of ADAM-12 expression under normal and osteoarthritic conditions | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Veterinary pathobiology (MU) | eng |
thesis.degree.grantor | University of Missouri--Columbia | eng |
thesis.degree.level | Masters | eng |
thesis.degree.name | M.S. | eng |