MISC

2012年1月

Pyruvate dehydrogenase kinase 4 induces bone loss at unloading by promoting osteoclastogenesis

BONE
  • Yuying Wang
  • Wenguang Liu
  • Ritsuko Masuyama
  • Ryo Fukuyama
  • Masako Ito
  • Quan Zhang
  • Hisato Komori
  • Tomohiko Murakami
  • Takeshi Moriishi
  • Toshihiro Miyazaki
  • Riko Kitazawa
  • Carolina A. Yoshida
  • Yosuke Kawai
  • Shinichi Izumi
  • Toshihisa Komori
  • 全て表示

50
1
開始ページ
409
終了ページ
419
記述言語
英語
掲載種別
DOI
10.1016/j.bone.2011.07.012
出版者・発行元
ELSEVIER SCIENCE INC

Disuse osteoporosis, which occurs commonly in prolonged bed rest and immobilization, is becoming a major problem in modern societies; however, the molecular mechanisms underlying unloading-driven bone loss have not been fully elucidated. The osteocyte network is considered to be an ideal mechanosensor and mechanotransduction system. We searched for the molecules responsible for disuse osteoporosis using BCL2 transgenic mice, in which the osteocyte network was disrupted. Pyruvate dehydrogenase kinase 4 (Pdk4), which inactivates pyruvate dehydrogenase complex (PDC), was upregulated in femurs and tibiae of wild-type mice but not of BCL2 transgenic mice after tail suspension. Bone in Pdk4(-/-) mice developed normally and was maintained. At unloading, however, bone mass was reduced due to enhanced osteoclastogenesis and Rankl expression in wild-type mice but not in Pdk4(-/-) mice. Osteoclast differentiation of Pdk4(-/-) bone marrow-derived monocyte/macrophage lineage cells (BMMs) in the presence of M-CSF and RANKL was suppressed, and osteoclastogenesis was impaired in the coculture of wild-type BMMs and Pdk4(-/-) osteoblasts, in which Rankl expression and promoter activity were reduced. Further, introduction of Pdk4 into Pdk4(-/-) BMMs and osteoblasts enhanced osteoclastogenesis and Rankl expression and activated Rankl promoter. These findings indicate that Pdk4 plays an important role in bone loss at unloading by promoting osteoclastogenesis. (C) 2011 Elsevier Inc. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.bone.2011.07.012
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000299064200053&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.bone.2011.07.012
  • ISSN : 8756-3282
  • Web of Science ID : WOS:000299064200053

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