ダウンロード数 : ?
ファイル
言語
英語
著者
横本 真希
内容記述(抄録等)
Background: AMP-activated protein kinase (AMPK) plays important roles in bone metabolism; however, little is known about its role in osteocytes. This study investigated the effects of AMPK activation on the expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in osteocytes.
Results: Real-time PCR showed that AMPK activation by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) significantly decreased the expression of Rankl in a dose- and time-dependent manner and significantly increased the expression of Sost, the gene encoding sclerostin, in osteocytic MLO-Y4 cells. Western blotting confirmed that AICAR decreased RANKL protein levels and increased sclerostin levels. In addition, suppression of AMPKα1 by siRNA significantly increased the expression of Rankl on 4 days after the transfection of siRNA, while Sost expression was not changed. Simvastatin, an inhibitor of HMG-CoA reductase, significantly decreased Rankl expression and increased Sost expression in MLO-Y4 cells. Supplementation with mevalonate or geranylgeranyl pyrophosphate, which are downstream metabolites of HMG-CoA reductase, significantly reversed the effects of AICAR.
Conclusion: These findings indicated that AMPK regulated RANKL and sclerostin expression through the mevalonate pathway in osteocytes.
主題
AMP-activated protein kinase
Osteocyte
RANKL
Sclerostin
Mevalonate pathway
掲載誌名
Biochemical and biophysical research communications
469
4
開始ページ
791
終了ページ
796
ISSN
0006291X
発行日
2016-01-22
DOI
DOI公開日
2017-04-11
PubMed ID
出版者
Elsevier
資料タイプ
学術雑誌論文
ファイル形式
PDF
権利関係
© 2015 Elsevier Inc. All rights reserved.
著者版/出版社版
著者版
業績ID
e28542
e28630
部局
医学部
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