JunB as a potential mediator of PTHrP actions: new gene targets Ephrin B1 and VCAM-1.
Oral Dis
; 14(8): 713-26, 2008 Nov.
Article
in En
| MEDLINE
| ID: mdl-19193201
ABSTRACT
Parathyroid hormone-related protein (PTHrP) is an integral mediator of physiologic and pathologic processes and has demonstrated actions in the periodontium. PTHrP functions via AP-1, and specifically through JunB. This study identified JunB-dependent downstream mediators of PTHrP using OCCM cementoblastic transfectants with JunB over- or reduced expression. Over-expressing cells showed an increase in proliferation, while the opposite was seen in siRNA transfected cells. Microarray analysis of over-expressing cells revealed more than 1000 regulated genes. Three genes were investigated in more detail. The PTH/PTHrP receptor (PTHR1) and ephrin B1 (EfnB1) were down-regulated, and vascular cell adhesion molecule-1 (VCAM-1) was up-regulated with JunB over-expression. JunB siRNA transfectants had increased PTHR1, but reduced ephrin B1 and unaltered VCAM-1 in vitro. To validate these targets, parental OCCM cells and primary osteoblasts were treated with PTHrP, resulting in reduced PTHR1 and ephrin B1, and increased VCAM-1. Cell transfectants were implanted subcutaneously in vivo, and microarray analysis and RT-PCR performed. Over-expression of JunB down-regulated PTHR1 and ephrin B1, and increased VCAM-1. JunB siRNA transfectant implants had increased PTHR1 and ephrin B1, but no altered VCAM-1. These data highlight new gene targets for PTHrP and indicate JunB is a critical mediator of PTHrP actions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-jun
/
Vascular Cell Adhesion Molecule-1
/
Ephrin-B1
/
Parathyroid Hormone-Related Protein
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Oral Dis
Journal subject:
ODONTOLOGIA
Year:
2008
Document type:
Article
Affiliation country:
United States