Genomewide comprehensive analysis reveals critical cooperation between smad and c-Fos in RANKL-induced osteoclastogenesis

Yasunori Omata, Tetsuro Yasui, Jun Hirose, Naohiro Izawa, Yuuki Imai, Takumi Matsumoto, Hironari Masuda, Naoto Tokuyama, Shinya Nakamura, Shuichi Tsutsumi, Hisataka Yasuda, Kazuo Okamoto, Hiroshi Takayanagi, Atsuhiko Hikita, Takeshi Imamura, Koichi Matsuo, Taku Saito, Yuho Kadono, Hiroyuki Aburatani, Sakae Tanaka

研究成果: Article査読

29 被引用数 (Scopus)

抄録

We have previously reported that transforming growth factor β (TGF-β) plays an essential role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. However, the detailed underlying molecular mechanisms still remain unclear. Formaldehyde-assisted isolation of regulatory elements (FAIRE) and chromatin immunoprecipitation (ChIP) followed by sequencing (FAIRE-seq and ChIP-seq) analyses indicated the cooperation of Smad2/3 with c-Fos during osteoclastogenesis. Biochemical analysis and immunocytochemical analysis revealed that physical interaction between Smad2/3 and c-Fos is required for their nuclear translocation. The gene expression of nuclear factor of activated T-cells, cytoplasmic 1 (Nfatc1), a key regulator of osteoclastogenesis, was regulated by RANKL and TGF-β, and c-Fos binding to open chromatin sites was suppressed by inhibition of TGF-β signaling by SB431542. Conversely, Smad2/3 binding to Nfatc1 was impaired by c-Fos deficiency. These results suggest that TGF-β regulates RANKL-induced osteoclastogenesis through reciprocal cooperation between Smad2/3 and c-Fos.

本文言語English
ページ(範囲)869-877
ページ数9
ジャーナルJournal of Bone and Mineral Research
30
5
DOI
出版ステータスPublished - 2015 5月 1

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 整形外科およびスポーツ医学

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