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Accelerated lactate dehydrogenase activity potentiates osteoclastogenesis via NFATc1 signaling

Title
Accelerated lactate dehydrogenase activity potentiates osteoclastogenesis via NFATc1 signaling
Authors
Ahn H.Lee K.Kim J.M.Kwon S.H.Lee S.H.Lee S.Y.Jeong D.
Ewha Authors
이수영
SCOPUS Author ID
이수영scopus
Issue Date
2016
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 11, no. 4
Publisher
Public Library of Science
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Osteoclasts seem to be metabolic active during their differentiation and bone-resorptive activation. However, the functional role of lactate dehydrogenase (LDH), a tetrameric enzyme consisting of an A and/or B subunit that catalyzes interconversion of pyruvate to lactate, in RANKL-induced osteoclast differentiation is not known. In this study, RANKL treatment induced gradual gene expression and activation of the LDH A2 B2 isotype during osteoclast differentiation as well as the LDH A1 B3 and B4 isotypes during osteoclast maturation after pre-osteoclast formation. Glucose consumption and lactate production in growth media were accelerated during osteoclast differentiation, together with enhanced expression of H+ -lactate co-transporter and increased extracellular acidification, demonstrating that glycolytic metabolism was stimulated during differentiation. Further, oxygen consumption via mitochondria was stimulated during osteoclast differentiation. On the contrary, depletion of LDH-A or LDH-B subunit suppressed both glycolytic and mitochondrial metabolism, resulting in reduced mature osteoclast formation via decreased osteoclast precursor fusion and down-regulation of the osteoclastogenic critical transcription factor NFATc1 and its target genes. Collectively, our findings suggest that RANKL-induced LDH activation stimulates glycolytic and mitochondrial respiratory metabolism, facilitating mature osteoclast formation via osteoclast precursor fusion and NFATc1 signaling. © 2016 Ahn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI
10.1371/journal.pone.0153886
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자연과학대학 > 생명과학전공 > Journal papers
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