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Bone. 2014 Apr;61:10-8. doi: 10.1016/j.bone.2013.12.028. Epub 2014 Jan 2.

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

Author information

  • 1Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
  • 2Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
  • 3Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea.
  • 4Department of Pharmacology and Dental Therapeutics and Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju 500-757, Republic of Korea.
  • 5Department of Biotechnology, School of Engineering, Daegu University, Gyeongbuk 712-714, Republic of Korea. Electronic address: jangwg@daegu.ac.kr.
  • 6Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea. Electronic address: jwlee@kribb.re.kr.

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

BMP2; Osteoblast; Osteocalcin; Runx2; SMILE

PMID:
24389415
[PubMed - indexed for MEDLINE]
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