ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone
Annual rept. 1 Jul 2007-30 Jun 2008
PITTSBURGH UNIV PA
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During the last year of support from July 1, 2007 to June 30, 2008, our studies have made significant progresses in all aspects of the study i we demonstrate that PTH increases ATF4 expression and activity and ATF4 is required for PTH induction of Ocn expression in osteoblasts. ATF4 is a novel downstream target of PTH signaling in osteoblasts ii we show that ATF4 is required for the anabolic actions of PTH on bone in vivo, these results were orally presented at the 2007 ASBMR American Society for Bone and Mineral Research annual meeting and iii We also shows that TFIIA gamma increases osteoblast-specific gene expression by facilitating ATF4-Runx2 interactions Taken together, these data further strongly support our original hypothesis and the specific aims. Two peer-reviewed research papers and two national meeting abstracts are generated from this study during this period of support. In the next year of support, we will i determine if ATF4 is required for the anabolic actions of PTH on bone in greater detail ii determine if ATF4 is required for PTH regulations of cell proliferation and apoptosis in vitro and in vivo and iii determine the role of ATF4-Runx2 interactions in PTH-induced osteoblast function.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research