Activation of AMP-activated protein kinase decreases receptor activator of NF-κB ligand expression and increases sclerostin expression by inhibiting the mevalonate pathway in osteocytic MLO-Y4 cells

Maki Yokomoto-Umakoshi, Ippei Kanazawa, Ayumu Takeno, Ken Ichiro Tanaka, Masakazu Notsu, Toshitsugu Sugimoto

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)791-796
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume469
Issue number4
DOIs
Publication statusPublished - Jan 22 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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