The orphan nuclear receptor estrogen receptor-related receptor γ negatively regulates BMP2-induced osteoblast differentiation and bone formation

Byung Chul Jeong, Yong Soo Lee, Yun Yong Park, In Ho Bae, Don Kyu Kim, Seung-Hoi Koo, Hong Ran Choi, Sun Hun Kim, Renny T. Franceschi, Jeong Tae Koh, Hueng Sik Choi

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Estrogen receptor-related receptor γ (ERRγ/ERR3/NR3B3) is a member of the orphan nuclear receptor with important functions in development and homeostasis. Recently it has been reported that ERRα is involved in osteoblast differentiation and bone formation. In the present study we examined the role of ERRγ in osteoblast differentiation. Here, we showed that ERRγ is expressed in osteoblast progenitors and primary osteoblasts, and its expression is increased temporarily by BMP2. Overexpression of ERRγ reduced BMP2-induced alkaline phosphatase activity and osteocalcin production as well as calcified nodule formation, whereas inhibition of ERRγ expression significantly enhanced BMP2-induced osteogenic differentiation and mineralization, suggesting that endogenous ERRγ plays an important role in osteoblast differentiation. In addition, ERRγ significantly repressed Runx2 transactivity on osteocalcin and bone sialoprotein promoters. We also observed that ERRγ physically interacts with Runx2 in vitro and in vivo and competes with p300 to repress Runx2 transactivity. Notably, intramuscular injection of ERRγ strongly inhibited BMP2-induced ectopic bone formation in a dose-dependent manner. Taken together, these results suggest that ERRγ is a novel negative regulator of osteoblast differentiation and bone formation via its regulation of Runx2 transactivity.

Original languageEnglish
Pages (from-to)14211-14218
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number21
DOIs
Publication statusPublished - 2009 May 22
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'The orphan nuclear receptor estrogen receptor-related receptor γ negatively regulates BMP2-induced osteoblast differentiation and bone formation'. Together they form a unique fingerprint.

  • Cite this

    Jeong, B. C., Lee, Y. S., Park, Y. Y., Bae, I. H., Kim, D. K., Koo, S-H., Choi, H. R., Kim, S. H., Franceschi, R. T., Koh, J. T., & Choi, H. S. (2009). The orphan nuclear receptor estrogen receptor-related receptor γ negatively regulates BMP2-induced osteoblast differentiation and bone formation. Journal of Biological Chemistry, 284(21), 14211-14218. https://doi.org/10.1074/jbc.M808345200