ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone
Annual rept. 1 Jul 2008-30 Jun 2009
PITTSBURGH UNIV PA
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During the last year of support from July 1, 2008 to June 30, 2009, our studies have made significant progresses in all aspects of the study i we demonstrate that ATF4 increases the expression of cyclin D1, a key factor for cell cycle progression, and osteoblast proliferation ii we show that ATF4 prevents osteoblasts from apoptosis in cultured osteoblasts and bone iii we also show that PTH stimulation of osteoblast proliferation and survival is dependent upon the presence of ATF4 in vivo and iv we demonstrate that intermittent PTH stimulates the expression of Osx and osteoblast-specific gene expression. PTH fails to stimulate Osx expression in Atf4-- animals. One peer-reviewed research paper and two national meeting abstracts are generated directly from this study during this period of support. In the next year of support, we will i determine the molecular mechanism whereby ATF4 mediates PTH stimulation of Osx ii determine the molecular mechanism whereby ATF4 promotes osteoblast proliferation and survival and iii determine the role of ATF4-Runx2 interactions in PTH-induced osteoblast function.
- Anatomy and Physiology
- Medicine and Medical Research