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

doi:10.1002/jbmr.2418

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

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28 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	869-877
Number of pages	9
Journal	Journal of Bone and Mineral Research
Volume	30
Issue number	5
DOIs	https://doi.org/10.1002/jbmr.2418
Publication status	Published - 2015 May 1

Keywords

Cell/tissue signaling
Cytokines
Molecular pathways
Osteoclast
Transcription factors

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/jbmr.2418

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Omata, Y., Yasui, T., Hirose, J., Izawa, N., Imai, Y., Matsumoto, T., Masuda, H., Tokuyama, N., Nakamura, S., Tsutsumi, S., Yasuda, H., Okamoto, K., Takayanagi, H., Hikita, A., Imamura, T., Matsuo, K., Saito, T., Kadono, Y., Aburatani, H., & Tanaka, S. (2015). Genomewide comprehensive analysis reveals critical cooperation between smad and c-Fos in RANKL-induced osteoclastogenesis. Journal of Bone and Mineral Research, 30(5), 869-877. https://doi.org/10.1002/jbmr.2418

Omata, Y, Yasui, T, Hirose, J, Izawa, N, Imai, Y, Matsumoto, T, Masuda, H, Tokuyama, N, Nakamura, S, Tsutsumi, S, Yasuda, H, Okamoto, K, Takayanagi, H, Hikita, A, Imamura, T, Matsuo, K, Saito, T, Kadono, Y, Aburatani, H & Tanaka, S 2015, 'Genomewide comprehensive analysis reveals critical cooperation between smad and c-Fos in RANKL-induced osteoclastogenesis', Journal of Bone and Mineral Research, vol. 30, no. 5, pp. 869-877. https://doi.org/10.1002/jbmr.2418

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abstract = "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.",

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AU - Omata, Yasunori

AU - Yasui, Tetsuro

AU - Hirose, Jun

AU - Izawa, Naohiro

AU - Imai, Yuuki

AU - Matsumoto, Takumi

AU - Masuda, Hironari

AU - Tokuyama, Naoto

AU - Nakamura, Shinya

AU - Tsutsumi, Shuichi

AU - Yasuda, Hisataka

AU - Okamoto, Kazuo

AU - Takayanagi, Hiroshi

AU - Hikita, Atsuhiko

AU - Imamura, Takeshi

AU - Matsuo, Koichi

AU - Saito, Taku

AU - Kadono, Yuho

AU - Aburatani, Hiroyuki

AU - Tanaka, Sakae

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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