ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2009
- Accession Number
- ADA508520
Entities
People
- Guozhi Xiao
Organizations
- University of Pittsburgh