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Title: C-ABL promotes osteoblast expansion through BMP signaling pathways
Authors: KUA HUI YI
Keywords: senescence, BMPs, p16INK4a, Id1, osteoporosis, c-Abl
Issue Date: 8-Aug-2008
Citation: KUA HUI YI (2008-08-08). C-ABL promotes osteoblast expansion through BMP signaling pathways. ScholarBank@NUS Repository.
Abstract: A defect in stem cell renewal or progenitor cell expansion might cause aging related diseases such as osteoporosis. We report here that c-Abl-/-osteoblasts show premature senescence due to up-regulation of p16INK4a. p16INK4a expression can be regulated by BMPs, which are major regulators of bone remodeling, through Erk1/2 and Smad1/5/8-Id1 in opposing ways. c-Abl deficiency shunts BMP signaling from Smad1/5/8 to Erk1/2, leading to the up-regulation of p16INK4a. Further studies suggest that c-Abl regulates these two signaling events by phosphorylating BMPRIA mainly on Y453/467, which differentially influences its interaction with BMPRII and Tab1-Tak1 complex. These findings place c-Abl in BMP signaling pathways and establish its importance in osteoprogenitor expansion, linking osteoprogenitor senescence to senile osteoporosis.
Appears in Collections:Ph.D Theses (Open)

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