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Title 

SMILE inhibits BMP-2-induced expression of osteocalcin by suppressing the activity of the RUNX2 transcription factor in MC3T3E1 cells

Authors 

Hoon JangE J KimJae Kyung ParkDong Ern KimHyoung Joo KimW S SunS HwangK B OhJ T KohW G JangJeong Woong Lee

Publisher 

Elsevier

Issue Date 

2014

Citation 

Bone, vol. 61, no. 10, pp. 10-18

Keywords 

BMP2OsteoblastOsteocalcinRunx2SMILE

Abstract 

Small heterodimer partner interacting leucine zipper protein (SMILE) is an orphan nuclear receptor and a member of the bZIP family of proteins. Several recent studies have suggested that SMILE is a novel co-repressor that is involved in nuclear receptor signaling; however, the role of SMILE in osteoblast differentiation has not yet been elucidated. This study demonstrates that SMILE inhibits osteoblast differentiation by regulating the activity of Runt-related transcription factor-2 (RUNX2). Tunicamycin, an inducer of endoplasmic reticulum stress, stimulated SMILE expression. Bone morphogenetic protein-2-induced expression of alkaline phosphatase and osteocalcin, both of which are osteogenic genes, was suppressed by SMILE. The molecular mechanism by which SMILE affects osteocalcin expression was also determined. An immunoprecipitation assay revealed a physical interaction between SMILE and RUNX2 that significantly impaired the RUNX2-dependent activation of the osteocalcin gene. A ChIP assay revealed that SMILE repressed the ability of RUNX2 to bind to the osteocalcin gene promoter. Taken together, these findings demonstrate that SMILE negatively regulates osteocalcin via a direct interaction with RUNX2.

ISSN 

8756-3282

Link 

http://dx.doi.org/10.1016/j.bone.2013.12.028

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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