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File
language
eng
Author
Yokomoto-Umakosh, Maki
Description
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.
Subject
AMP-activated protein kinase
Osteocyte
RANKL
Sclerostin
Mevalonate pathway
Journal Title
Biochemical and biophysical research communications
Volume
469
Issue
4
Start Page
791
End Page
796
ISSN
0006291X
Published Date
2016-01-22
DOI
DOI Date
2017-04-11
PubMed ID
Publisher
Elsevier
NII Type
Journal Article
Format
PDF
Rights
© 2015 Elsevier Inc. All rights reserved.
Text Version
著者版
Gyoseki ID
e28542
e28630
OAI-PMH Set
Faculty of Medicine
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