ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone
Abstract
During the last year of support (from July 1, 2009 to June 30, 2010), our studies have made significant progresses in all aspects of the study: 1) we demonstrate that ATF4 is essential for PTH promotion of osteoblast differentiation in vivo; 2) we have identified and characterized an ATF4-response element in mouse Osx promoter that is essential for ATF4 to induce Osx expression in osteoblasts and probably osteoblast differentiation; 3) we demonstrate that ATF4 is required for the anabolic actions of PTH in bone in adult OVX mice; 4) we have established that ATF4 is important for intermittent PTH to stimulate osteoblast-mediated bone formation in vivo; 5) we have revealed that ATF4 is essential for OVX induction of bone loss in vivo; and 6) we have identified and functionally characterized Erk/MAPK phosphorylation sites in Runx2, an ATF4-interacting factor identified by the project laboratory. In the next year of support, we will: i) identify and characterize PTH response phosphorylation site in ATF4; 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, 2010
- Accession Number
- ADA541206
Entities
People
- Guozhi Xiao
Organizations
- University of Pittsburgh