ATF3 controls proliferation of osteoclast precursor and bone remodeling

Kazuya Fukasawa, Gyujin Park, Takashi Iezaki, Tetsuhiro Horie, Takashi Kanayama, Kakeru Ozaki, Yuki Onishi, Yoshifumi Takahata, Yukio Yoneda, Takeshi Takarada, Shigetaka Kitajima, Jean Vacher, Eiichi Hinoi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Bone homeostasis is maintained by the sophisticated coupled actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Here we identify activating transcription factor 3 (ATF3) as a pivotal transcription factor for the regulation of bone resorption and bone remodeling under a pathological condition through modulating the proliferation of osteoclast precursors. The osteoclast precursorspecific deletion of ATF3 in mice led to the prevention of receptor activator of nuclear factor-êB (RANK) ligand (RANKL)-induced bone resorption and bone loss, although neither bone volume nor osteoclastic parameter were markedly altered in these knockout mice under the physiological condition. RANKLdependent osteoclastogenesis was impaired in vitro in ATF3-deleted bone marrow macrophages (BMM). Mechanistically, the deficiency of ATF3 impaired the RANKL-induced transient increase in cell proliferation of osteoclast precursors in bone marrow in vivo as well as of BMM in vitro. Moreover, ATF3 regulated cyclin D1 mRNA expression though modulating activator protein-1-dependent transcription in the osteoclast precursor, and the introduction of cyclin D1 significantly rescued the impairment of osteoclastogenesis in ATF3-deleted BMM. Therefore, these findings suggest that ATF3 could have a pivotal role in osteoclastogenesis and bone homeostasis though modulating cell proliferation under pathological conditions, thereby providing a target for bone diseases.

Original languageEnglish
Article number30918
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Aug 2 2016
Externally publishedYes

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Activating Transcription Factor 3
Bone Remodeling
Osteoclasts
Bone and Bones
Bone Marrow
Osteogenesis
RANK Ligand
Cyclin D1
Macrophages
Bone Resorption
Homeostasis
Cell Proliferation
Bone Diseases
Transcription Factor AP-1
Cytoplasmic and Nuclear Receptors
Osteoblasts
Knockout Mice
Transcription Factors
Messenger RNA

ASJC Scopus subject areas

  • General

Cite this

Fukasawa, K., Park, G., Iezaki, T., Horie, T., Kanayama, T., Ozaki, K., ... Hinoi, E. (2016). ATF3 controls proliferation of osteoclast precursor and bone remodeling. Scientific Reports, 6, [30918]. https://doi.org/10.1038/srep30918

ATF3 controls proliferation of osteoclast precursor and bone remodeling. / Fukasawa, Kazuya; Park, Gyujin; Iezaki, Takashi; Horie, Tetsuhiro; Kanayama, Takashi; Ozaki, Kakeru; Onishi, Yuki; Takahata, Yoshifumi; Yoneda, Yukio; Takarada, Takeshi; Kitajima, Shigetaka; Vacher, Jean; Hinoi, Eiichi.

In: Scientific Reports, Vol. 6, 30918, 02.08.2016.

Research output: Contribution to journalArticle

Fukasawa, K, Park, G, Iezaki, T, Horie, T, Kanayama, T, Ozaki, K, Onishi, Y, Takahata, Y, Yoneda, Y, Takarada, T, Kitajima, S, Vacher, J & Hinoi, E 2016, 'ATF3 controls proliferation of osteoclast precursor and bone remodeling', Scientific Reports, vol. 6, 30918. https://doi.org/10.1038/srep30918
Fukasawa K, Park G, Iezaki T, Horie T, Kanayama T, Ozaki K et al. ATF3 controls proliferation of osteoclast precursor and bone remodeling. Scientific Reports. 2016 Aug 2;6. 30918. https://doi.org/10.1038/srep30918
Fukasawa, Kazuya ; Park, Gyujin ; Iezaki, Takashi ; Horie, Tetsuhiro ; Kanayama, Takashi ; Ozaki, Kakeru ; Onishi, Yuki ; Takahata, Yoshifumi ; Yoneda, Yukio ; Takarada, Takeshi ; Kitajima, Shigetaka ; Vacher, Jean ; Hinoi, Eiichi. / ATF3 controls proliferation of osteoclast precursor and bone remodeling. In: Scientific Reports. 2016 ; Vol. 6.
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