The role of FOXO1 in mesenchymal cells
Siqueira, Michelle Foigel
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New therapies can improve bone repair as well as preserve bone mass during aging. Understanding the mechanisms involved in the regulation of this process is essential for the future discovery of treatments that will lead to increased bone formation, improving the life quality of a significant part of the population. Forkhead Box O1A (FOXO1) is a transcription factor involved in the regulation of diverse cellular responses, such as apoptosis, cell cycle arrest and gluconeogenesis. FOXO1 is active in the nucleus and when phosphorylated by protein kinase B, remains inactive in the cytoplasm. To identify the relevance of FOXO1 during bone and cartilage formation and resorption in cells with mesenchymal origin, in vitro studies were carried out with murine osteoblastic cell line MC3T3-El, murine chondrocytic cell line ATDC5 and murine mesenchymal stem cell line C3H10Tl/2. MC3T3-El cells were treated with ascorbic acid and beta glycerophosphate. Increased FOXOl and runt-related transcription factor 2 DNA binding activity, alkaline phosphatase activity, formation of mineralized nodules, as well as mRNA level of bone markers was induced by mineralization. FOXO1 knock down by siRNA significantly diminished the increase caused by osteoblast differentiation in all the assays and this result was later confirmed by FOXO1 inhibition through shRNA at mRNA level. Further ... [TRUNCATED]
Thesis (D.Sc.D.)--Boston University, Goldman School of Dental Medicine, 2008 (Dept. of Periodontology and Oral Biology).Includes bibliography: leaves 177-195.
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