Effects of TNF-a on lysyl oxidase in Wnt induced cells at post-transcriptional level by miRNA
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Objective: Lysyl oxidase (LOX) dependent cross-linking is deficient in diabetic bone, contributing to osteopenia. Here we Investigate regulation of lysyl oxidase by Wnt3a and TNF-a in a mesenchymal stem cell line as a model for a novel mechanism of diabetic osteopenia. Methods: Wnt3a-treated C3Hl 0Tl/2 cells were treated with or without of TNF-a. Lysyl oxidase expression ( qPCR) and mRNA stability were measured. A comprehensive PCR-based microarray screen (Qiagen/SA Biosciences) was next performed to_ identify miRNAs which regulate LOX mRNA stability in response to TNF-a. The functionality of identified miRNA was independently determined by the use of miRNA mimics. Results: Wnt3a up-regulated LOX up to 3.2-fold by treating C3H10Tl/2 cells with Wnt3a compared to controls. TNF-a (20 ng/ml) blocked Wnt3a up-regulation of LOX. TNF-a decreased the stability of LOX mRNA determined in the presence of a transcription inhibitor in control- and Wnt3a plus TNF-a-treated cells. A micro (miR) array screen performed on RNA isolated from Wnt3a plus TNF-a treated and control cells identified miR203 as being up-regulated 13-fold by TNF-a. Independent analyses ... [TRUNCATED]
Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2013 (Department of Periodontology and Oral Biology).Includes bibliographic references: leaves 50-67.
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