The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone formation

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Title
The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone formation
Author(s)
B C Jeong; Y S Lee; I H Bae; Chul Ho Lee; H I Shin; H J Ha; R T Franceschi; H S Choi; J T Koh
Bibliographic Citation
Journal of Bone and Mineral Research, vol. 25, no. 2, pp. 262-274
Publication Year
2010
Abstract
The orphan nuclear receptor-small heterodimer partner (SHP; NR0B2) interacts with a diverse array of transcription factors and regulates a variety of cellular events such as cell proliferation, differentiation and metabolism. However, the role of SHP in bone formation has not yet been elucidated. SHP expression is significantly increased during osteoblast differentiation, and its expression is partially regulated by BMP2, which plays an important role in bone formation. In our study, inhibition of SHP expression significantly repressed BMP2-induced osteoblast differentiation and ectopic bone formation. In accordance with these in vitro and in vivo results, osteoblast differentiation in SHP-/- mice primary osteoblasts was significantly repressed, and the mice showed decreased bone mass resulting from decreased numbers of osteoblasts. Finally, SHP physically interacts and forms a complex with Runx2 on the osteocalcin gene promoter, and overexpression of SHP increased Runx2 transactivity via competition with HDAC4, an enzyme that inhibits DNA binding of Runx2 to its target genes. Taken together, these results indicate that SHP acts as a novel positive regulator of bone formation by augmenting osteoblast differentiation through regulation of the transcriptional activity of Runx2.
Keyword
BONE MORPHOGENETIC PROTEIN (BMP)RUNX2ORPHAN NUCLEAR RECEPTORSMALL HETERODIMER PARTNER (SHP)OSTEOBLAST DIFFERENTIATION
ISSN
0884-0431
Publisher
Wiley
DOI
http://dx.doi.org/10.1359/jbmr.090718
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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