Accession Number:

ADA550617

Title:

ATF4, A Novel Mediator of the Anabolic Actions of PTH on Bone

Descriptive Note:

Final rept. 1 Jul 2007-30 Jun 2011

Corporate Author:

PITTSBURGH UNIV PA

Personal Author(s):

Report Date:

2011-07-01

Pagination or Media Count:

105.0

Abstract:

In this study, we have successfully demonstrated that ATF4 plays a critical role in mediating the anabolic effects of intermittent PTH on bones. ATF4 is important for intermittent PTH to stimulate bone formation in mice. ATF4 favors bone formation through, at least in part, upregulation of osteoblasst proliferation and survival. Additionally, ATF4 increases osteoblast differentiation probably via osterix. At molecular level, ATF4 increases osteocalcin gene expression by cooperative interactions with TFIIA and Runx2. ATF4 increases the expression of cyclin D1, a key factor for cell cycle progression. We have identified and functionally characterized ErkMAPK phosphorylation sites in Runx2, an ATF4-interacting factor. We have demonstrated that ATF4 is essential for osteoclast differentiation and bone resorption, which is increased by intermittent PTH.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE