Bcl6 promotes osteoblastogenesis through stat1 inhibition

Atsuhiro Fujie, Atsushi Funayama, Yoshiteru Miyauchi, Yuiko Sato, Tami Kobayashi, Hiroya Kanagawa, Eri Katsuyama, Wu Hao, Toshimi Tando, Ryuichi Watanabe, Mayu Morita, Kana Miyamoto, Arihiko Kanaji, Hideo Morioka, Morio Matsumoto, Yoshiaki Toyama, Takeshi Miyamoto

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Bone mass is tightly controlled by a balance between osteoclast and osteoblast activities. Although these cell types mature via different pathways, some factors reportedly regulate differentiation of both. Here, in a search for factors governing osteoblastogenesis but also expressed in osteoclasts to control both cell types by one molecule, we identified B cell lymphoma 6 (Bcl6) as one of those factors and show that it promotes osteoblast differentiation. Bcl6 was previously shown to negatively regulate osteoclastogenesis. We report that lack of Bcl6 results in significant inhibition of osteoblastogensis in vivo and in vitro and in defects in secondary ossification center formation in vivo. Signal transducer and activator of transcription 1 (Stat1) reportedly attenuates osteoblast differentiation by inhibiting nuclear translocation of runt-related transcription factor 2 (Runx2), which is essential for osteoblast differentiation. We found that lack of Bcl6 resulted in signifi cant elevation of Stat1 mRNA and protein expression in osteoblasts and showed that Stat1 is a direct target of Bcl6 using a chromatin immune-precipitation assay. Mice lacking both Bcl6 and Stat1 (DKO) exhibited significant rescue of bone mass and osteoblastic parameters as well as partial rescue of secondary ossification center formation compared with Bcl6-de ficient mice in vivo. Altered osteoblastogenesis in Bcl6-defi cient cells was also restored in DKO in vitro. Thus, Bcl6 plays crucial roles in regulating both osteoblast activation and osteoclast inhibition.

Original languageEnglish
Pages (from-to)451-456
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume457
Issue number3
DOIs
Publication statusPublished - 2015 Feb 13

Keywords

  • Bcl6
  • Bone
  • Differentiation
  • Osteoblast
  • Stat1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Fujie, A., Funayama, A., Miyauchi, Y., Sato, Y., Kobayashi, T., Kanagawa, H., Katsuyama, E., Hao, W., Tando, T., Watanabe, R., Morita, M., Miyamoto, K., Kanaji, A., Morioka, H., Matsumoto, M., Toyama, Y., & Miyamoto, T. (2015). Bcl6 promotes osteoblastogenesis through stat1 inhibition. Biochemical and Biophysical Research Communications, 457(3), 451-456. https://doi.org/10.1016/j.bbrc.2015.01.012