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Title: Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling

Abstract

Cytosolic malate dehydrogenase (malate dehydrogenase 1, MDH1) plays pivotal roles in the malate/aspartate shuttle that might modulate metabolism between the cytosol and mitochondria. In this study, we investigated the role of MDH1 in osteoclast differentiation and formation. MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. Knockdown of MDH1 by infection with retrovirus containing MDH1-specific shRNA (shMDH1) reduced mature osteoclast formation and bone resorption activity. Moreover, the expression of marker genes associated with osteoclast differentiation was downregulated by shMDH1 treatment, suggesting a role of MDH1 in osteoclast differentiation. In addition, intracellular ATP production was reduced following the activation of adenosine 5′ monophosphate-activated protein kinase (AMPK), a cellular energy sensor and negative regulator of RANKL-induced osteoclast differentiation, in shMDH1-infected osteoclasts compared to control cells. In addition, the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor of osteoclastogenesis, was decreased with MDH1 knockdown during RANKL-mediated osteoclast differentiation. These findings provide strong evidence that MDH1 plays a critical role in osteoclast differentiation and function via modulation of the intracellular energy status, which might affect AMPK activity and NFATc1 expression.

Authors:
 [1];  [1];  [2];  [3];  [1];  [2];  [1];  [2];  [4]
  1. Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of)
  2. (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of)
  3. Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of)
  4. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22598772
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 475; Journal Issue: 1; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADENOSINE; ATP; LIGANDS; METABOLISM; MITOCHONDRIA; MODULATION; RABBIT TUBES; RECEPTORS; SENSORS; SKELETON; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Oh, Se Jeong, Gu, Dong Ryun, Center for Metabolic Function Regulation, Jin, Su Hyun, Park, Keun Ha, Center for Metabolic Function Regulation, Lee, Seoung Hoon, E-mail: leesh2@wku.ac.kr, Center for Metabolic Function Regulation, and Wonkwang Institute of Biomaterials and Implant, Wonkwang University, Iksan, Jeonbuk 54538. Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.05.055.
Oh, Se Jeong, Gu, Dong Ryun, Center for Metabolic Function Regulation, Jin, Su Hyun, Park, Keun Ha, Center for Metabolic Function Regulation, Lee, Seoung Hoon, E-mail: leesh2@wku.ac.kr, Center for Metabolic Function Regulation, & Wonkwang Institute of Biomaterials and Implant, Wonkwang University, Iksan, Jeonbuk 54538. Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling. United States. doi:10.1016/J.BBRC.2016.05.055.
Oh, Se Jeong, Gu, Dong Ryun, Center for Metabolic Function Regulation, Jin, Su Hyun, Park, Keun Ha, Center for Metabolic Function Regulation, Lee, Seoung Hoon, E-mail: leesh2@wku.ac.kr, Center for Metabolic Function Regulation, and Wonkwang Institute of Biomaterials and Implant, Wonkwang University, Iksan, Jeonbuk 54538. Fri . "Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling". United States. doi:10.1016/J.BBRC.2016.05.055.
@article{osti_22598772,
title = {Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling},
author = {Oh, Se Jeong and Gu, Dong Ryun and Center for Metabolic Function Regulation and Jin, Su Hyun and Park, Keun Ha and Center for Metabolic Function Regulation and Lee, Seoung Hoon, E-mail: leesh2@wku.ac.kr and Center for Metabolic Function Regulation and Wonkwang Institute of Biomaterials and Implant, Wonkwang University, Iksan, Jeonbuk 54538},
abstractNote = {Cytosolic malate dehydrogenase (malate dehydrogenase 1, MDH1) plays pivotal roles in the malate/aspartate shuttle that might modulate metabolism between the cytosol and mitochondria. In this study, we investigated the role of MDH1 in osteoclast differentiation and formation. MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. Knockdown of MDH1 by infection with retrovirus containing MDH1-specific shRNA (shMDH1) reduced mature osteoclast formation and bone resorption activity. Moreover, the expression of marker genes associated with osteoclast differentiation was downregulated by shMDH1 treatment, suggesting a role of MDH1 in osteoclast differentiation. In addition, intracellular ATP production was reduced following the activation of adenosine 5′ monophosphate-activated protein kinase (AMPK), a cellular energy sensor and negative regulator of RANKL-induced osteoclast differentiation, in shMDH1-infected osteoclasts compared to control cells. In addition, the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor of osteoclastogenesis, was decreased with MDH1 knockdown during RANKL-mediated osteoclast differentiation. These findings provide strong evidence that MDH1 plays a critical role in osteoclast differentiation and function via modulation of the intracellular energy status, which might affect AMPK activity and NFATc1 expression.},
doi = {10.1016/J.BBRC.2016.05.055},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 475,
place = {United States},
year = {Fri Jun 17 00:00:00 EDT 2016},
month = {Fri Jun 17 00:00:00 EDT 2016}
}