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

13 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

Fingerprint

Osteoblasts
B-Cell Lymphoma
STAT1 Transcription Factor
Osteoclasts
Osteogenesis
Bone
STAT Transcription Factors
Chromatin
Bone and Bones
Assays
Transcription Factors
Chemical activation
Cells
Immunoprecipitation
Messenger RNA
Defects
Molecules
Proteins

Keywords

  • Bcl6
  • Bone
  • Differentiation
  • Osteoblast
  • Stat1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Fujie, A., Funayama, A., Miyauchi, Y., Sato, Y., Kobayashi, T., Kanagawa, H., ... 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

Bcl6 promotes osteoblastogenesis through stat1 inhibition. / Fujie, Atsuhiro; Funayama, Atsushi; Miyauchi, Yoshiteru; Sato, Yuiko; Kobayashi, Tami; Kanagawa, Hiroya; Katsuyama, Eri; Hao, Wu; Tando, Toshimi; Watanabe, Ryuichi; Morita, Mayu; Miyamoto, Kana; Kanaji, Arihiko; Morioka, Hideo; Matsumoto, Morio; Toyama, Yoshiaki; Miyamoto, Takeshi.

In: Biochemical and Biophysical Research Communications, Vol. 457, No. 3, 13.02.2015, p. 451-456.

Research output: Contribution to journalArticle

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, vol. 457, no. 3, pp. 451-456. https://doi.org/10.1016/j.bbrc.2015.01.012
Fujie A, Funayama A, Miyauchi Y, Sato Y, Kobayashi T, Kanagawa H et al. Bcl6 promotes osteoblastogenesis through stat1 inhibition. Biochemical and Biophysical Research Communications. 2015 Feb 13;457(3):451-456. https://doi.org/10.1016/j.bbrc.2015.01.012
Fujie, Atsuhiro ; Funayama, Atsushi ; Miyauchi, Yoshiteru ; Sato, Yuiko ; Kobayashi, Tami ; Kanagawa, Hiroya ; Katsuyama, Eri ; Hao, Wu ; Tando, Toshimi ; Watanabe, Ryuichi ; Morita, Mayu ; Miyamoto, Kana ; Kanaji, Arihiko ; Morioka, Hideo ; Matsumoto, Morio ; Toyama, Yoshiaki ; Miyamoto, Takeshi. / Bcl6 promotes osteoblastogenesis through stat1 inhibition. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 457, No. 3. pp. 451-456.
@article{7af20a1bf45044de8a52cb519438302c,
title = "Bcl6 promotes osteoblastogenesis through stat1 inhibition",
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.",
keywords = "Bcl6, Bone, Differentiation, Osteoblast, Stat1",
author = "Atsuhiro Fujie and Atsushi Funayama and Yoshiteru Miyauchi and Yuiko Sato and Tami Kobayashi and Hiroya Kanagawa and Eri Katsuyama and Wu Hao and Toshimi Tando and Ryuichi Watanabe and Mayu Morita and Kana Miyamoto and Arihiko Kanaji and Hideo Morioka and Morio Matsumoto and Yoshiaki Toyama and Takeshi Miyamoto",
year = "2015",
month = "2",
day = "13",
doi = "10.1016/j.bbrc.2015.01.012",
language = "English",
volume = "457",
pages = "451--456",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Bcl6 promotes osteoblastogenesis through stat1 inhibition

AU - Fujie, Atsuhiro

AU - Funayama, Atsushi

AU - Miyauchi, Yoshiteru

AU - Sato, Yuiko

AU - Kobayashi, Tami

AU - Kanagawa, Hiroya

AU - Katsuyama, Eri

AU - Hao, Wu

AU - Tando, Toshimi

AU - Watanabe, Ryuichi

AU - Morita, Mayu

AU - Miyamoto, Kana

AU - Kanaji, Arihiko

AU - Morioka, Hideo

AU - Matsumoto, Morio

AU - Toyama, Yoshiaki

AU - Miyamoto, Takeshi

PY - 2015/2/13

Y1 - 2015/2/13

N2 - 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.

AB - 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.

KW - Bcl6

KW - Bone

KW - Differentiation

KW - Osteoblast

KW - Stat1

UR - http://www.scopus.com/inward/record.url?scp=84922738990&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922738990&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2015.01.012

DO - 10.1016/j.bbrc.2015.01.012

M3 - Article

VL - 457

SP - 451

EP - 456

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 3

ER -