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Musculoskeletal Phenotype of Egr-1 Deficient Mice

Posted on:2011-03-18Degree:M.ScType:Thesis
University:McGill University (Canada)Candidate:Debiparshad, KevinFull Text:PDF
GTID:2444390002961268Subject:Biology
Abstract/Summary:
Early growth response protein-1 (EGR-1) is a transcription factor induced by stress or injury, mitogens, and differentiation factors. It has been shown to be regulated by various cytokines, growth factors and by ischemic/hypoxic stress as well as shear stress and mechanical injury. These regulators have been linked to both the development as well the degeneration of the musculoskeletal system, namely articular cartilage, intervertebral discs (IVDs) and bone. Furthermore, Egr-1 has been shown to regulate the expression of collagens and enzymes affecting the extracellular matrix. Polymorphisms of DNA binding sites for EGR-1 have shown to be associated with both disc degeneration and osteoporosis. The aim of this study was to determine the affects of EGR-1 deficiency on articular cartilage, IVD and bone phenotype.;Results revealed that these mice have differences including abnormal bone structure and density, structural and possibly compositional differences in articular cartilage and structural and biochemical changes in IVDs. This points to the importance of Egr-1 in the maintenance of normal bone, IVD and articular cartilage and makes it a possible target for initiating pathological conditions of these tissues.;Wild-type (+/+) C57Bl/6 or Egr-1-deficient (-/-) mice were sacrificed at the same age interval (8- to 9-months). Standard histological preparation and staining with Safranin-O/Fast Green were done. Also immuncohistochemistry was performed using anti-bodies to type X collagen, cleavage products of both type II collagen and aggrecan. Imaging of mice was with plain radiographs, bone mineral density measurements and microCT analysis.
Keywords/Search Tags:EGR-1, Mice, Articular cartilage
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