Suppression by HSP90 inhibitors of BMP‑4‑stimulated osteoprotegerin synthesis in osteoblasts: Attenuation of p70 S6 kinase

  • Authors:
    • Tetsu Kawabata
    • Takanobu Otsuka
    • Kazuhiko Fujita
    • Shingo Kainuma
    • Naohiro Yamamoto
    • Gen Kuroyanagi
    • Go Sakai
    • Rie Matsushima‑Nishiwaki
    • Osamu Kozawa
    • Haruhiko Tokuda
  • View Affiliations

  • Published online on: September 27, 2017     https://doi.org/10.3892/mmr.2017.7639
  • Pages:8507-8512
0

Abstract

Heat shock protein 90 (HSP90) is an ATP‑dependent ubiquitous molecular chaperon which is important in cell homeostasis. The authors previously demonstrated that bone morphogenetic protein (BMP)‑4 stimulates osteoprotegerin (OPG) production in osteoblast‑like MC3T3‑E1 cells, and that p70 S6 kinase positively regulates the OPG synthesis by BMP‑4. The present study investigated the involvement of HSP90 in the BMP‑4‑stimulated OPG synthesis and the mechanism in MC3T3‑E1 cells. HSP90 inhibitors, 17‑allylamino‑17demethoxy‑geldanamycin (17‑AAG), 17‑dimethylamino‑ethylamino‑17‑demethoxy‑geldanamycin (17‑DMAG) and geldanamycin significantly suppressed the BMP‑4‑stimulated OPG release. Geldanamycin markedly reduced the BMP‑4‑induced mRNA expression of OPG. 17‑AAG and 17‑DMAG significantly attenuated the phosphorylation of p70 S6 kinase induced by BMP‑4 without affecting the BMP‑4‑induced phosphorylation of mothers against decapentaplegic homolog 1/5. The results suggest that HSP90 inhibitors suppress the BMP‑4‑stimulated OPG synthesis in osteoblasts, and that their suppressive effects are exerted through downregulating p70 S6 kinase.

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December 2017
Volume 16 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Kawabata, T., Otsuka, T., Fujita, K., Kainuma, S., Yamamoto, N., Kuroyanagi, G. ... Tokuda, H. (2017). Suppression by HSP90 inhibitors of BMP‑4‑stimulated osteoprotegerin synthesis in osteoblasts: Attenuation of p70 S6 kinase. Molecular Medicine Reports, 16, 8507-8512. https://doi.org/10.3892/mmr.2017.7639
MLA
Kawabata, T., Otsuka, T., Fujita, K., Kainuma, S., Yamamoto, N., Kuroyanagi, G., Sakai, G., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."Suppression by HSP90 inhibitors of BMP‑4‑stimulated osteoprotegerin synthesis in osteoblasts: Attenuation of p70 S6 kinase". Molecular Medicine Reports 16.6 (2017): 8507-8512.
Chicago
Kawabata, T., Otsuka, T., Fujita, K., Kainuma, S., Yamamoto, N., Kuroyanagi, G., Sakai, G., Matsushima‑Nishiwaki, R., Kozawa, O., Tokuda, H."Suppression by HSP90 inhibitors of BMP‑4‑stimulated osteoprotegerin synthesis in osteoblasts: Attenuation of p70 S6 kinase". Molecular Medicine Reports 16, no. 6 (2017): 8507-8512. https://doi.org/10.3892/mmr.2017.7639