A microRNA regulatory mechanism of osteoblast differentiation

Hiroyuki Inose, Hiroki Ochi, Ayako Kimura, Koji Fujita, Ren Xu, Shingo Sato, Makiko Iwasaki, Satoko Sunamura, Yasuhiro Takeuchi, Seiji Fukumoto, Kuniaki Saito, Takashi Nakamura, Haruhiko Siomi, Hiroshi Itoh, Yoshiyasu Arai, Ken Ichi Shinomiya, Shu Takeda

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

Growing evidence shows that microRNAs (miRNAs) regulate various developmental and homeostatic events in vertebrates and invertebrates. Osteoblast differentiation is a key step in proper skeletal development and acquisition of bone mass; however, the physiological role of non-coding small RNAs, especially miRNAs, in osteoblast differentiation remains elusive. Here, through comprehensive analysis of miRNAs expression during osteoblast differentiation, we show that miR-206, previously viewed as a muscle-specific miRNA, is a key regulator of this process. miR-206 was expressed in osteoblasts, and its expression decreased over the course of osteoblast differentiation. Overexpression of miR-206 in osteoblasts inhibited their differentiation, and conversely, knockdown of miR-206 expression promoted osteoblast differentiation. In silico analysis and molecular experiments revealed connexin 43 (Cx43), a major gap junction protein in osteoblasts, as a target of miR-206, and restoration of Cx43 expression in miR-206-expressing osteoblasts rescued them from the inhibitory effect of miR-206 on osteoblast differentiation. Finally, transgenic mice expressing miR-206 in osteoblasts developed a low bone mass phenotype due to impaired osteoblast differentiation. Our data show that miRNA is a regulator of osteoblast differentiation.

Original languageEnglish
Pages (from-to)20794-20799
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number49
DOIs
Publication statusPublished - 2009 Dec 8

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Osteoblasts
MicroRNAs
Connexin 43
Small Untranslated RNA
Connexins
Bone Development
Invertebrates
Computer Simulation
Transgenic Mice
Vertebrates

Keywords

  • Connexin43
  • mIR-206

ASJC Scopus subject areas

  • General

Cite this

A microRNA regulatory mechanism of osteoblast differentiation. / Inose, Hiroyuki; Ochi, Hiroki; Kimura, Ayako; Fujita, Koji; Xu, Ren; Sato, Shingo; Iwasaki, Makiko; Sunamura, Satoko; Takeuchi, Yasuhiro; Fukumoto, Seiji; Saito, Kuniaki; Nakamura, Takashi; Siomi, Haruhiko; Itoh, Hiroshi; Arai, Yoshiyasu; Shinomiya, Ken Ichi; Takeda, Shu.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 49, 08.12.2009, p. 20794-20799.

Research output: Contribution to journalArticle

Inose, H, Ochi, H, Kimura, A, Fujita, K, Xu, R, Sato, S, Iwasaki, M, Sunamura, S, Takeuchi, Y, Fukumoto, S, Saito, K, Nakamura, T, Siomi, H, Itoh, H, Arai, Y, Shinomiya, KI & Takeda, S 2009, 'A microRNA regulatory mechanism of osteoblast differentiation', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 49, pp. 20794-20799. https://doi.org/10.1073/pnas.0909311106
Inose, Hiroyuki ; Ochi, Hiroki ; Kimura, Ayako ; Fujita, Koji ; Xu, Ren ; Sato, Shingo ; Iwasaki, Makiko ; Sunamura, Satoko ; Takeuchi, Yasuhiro ; Fukumoto, Seiji ; Saito, Kuniaki ; Nakamura, Takashi ; Siomi, Haruhiko ; Itoh, Hiroshi ; Arai, Yoshiyasu ; Shinomiya, Ken Ichi ; Takeda, Shu. / A microRNA regulatory mechanism of osteoblast differentiation. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 49. pp. 20794-20799.
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