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Overexpressing Galphas in Osteoblasts in vitro and in vivo: Effects on Basal and PTH-Stimulated Gene Expression

Posted on:2015-09-18Degree:M.ScType:Thesis
University:University of Toronto (Canada)Candidate:Claridge, ColinFull Text:PDF
GTID:2474390020951771Subject:Pharmacology
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Previous work in our laboratory showed altered signaling through the parathyroid hormone (PTH) receptor when Galpha11 was overexpressed in osteoblasts. To examine the effect of Galphas overexpression on PTH signaling, we transfected Gas long into UMR osteoblastic cells and generated transgenic mice overexpressing Galphas in osteoblasts. Transfected UMR cells displayed elevated Galphas but no changes in basal or PTH stimulated gene expression compared to control cells. A transgenic mouse line was generated with elevated Galphas long expression specifically within bone and not other tissues. Runx2 mRNA was increased 52% in neonatal calvaria from transgenic mice but PTH stimulated gene expression was not different from that in wild-type calvaria. In summary, overexpression of Galphas long in osteoblasts in vitro and in vivo resulted in no changes in PTH response. Increased Runx2 expression in bone of +Galphas mice requires further studies to characterize potential changes in bone development in this mouse line.
Keywords/Search Tags:PTH, Galphas, Osteoblasts, Expression, Gene
PDF Full Text Request
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