破骨细胞
兰克尔
糖酵解
乳酸脱氢酶
细胞分化
细胞生物学
化学
乳酸脱氢酶A
生物
生物化学
新陈代谢
酶
激活剂(遗传学)
受体
基因
作者
Heejin Ahn,Kyung‐Hee Lee,Jin‐Man Kim,So Hyun Kwon,Seoung Hoon Lee,Soo Young Lee,Daewon Jeong
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2016-04-14
卷期号:11 (4): e0153886-e0153886
被引量:38
标识
DOI:10.1371/journal.pone.0153886
摘要
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 A2B2 isotype during osteoclast differentiation as well as the LDH A1B3 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.
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