KMID : 0811720190230050411
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Korean Journal of Physiology & Pharmacology 2019 Volume.23 No. 5 p.411 ~ p.417
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Humanin suppresses receptor activator of nuclear factor-¥êB ligand-induced osteoclast differentiation via AMP-activated protein kinase activation
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Kang Nam-Ju
Kim Ki-Woo Shin Dong-Min
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Abstract
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Humanin (HN) is a mitochondrial peptide that exhibits cytoprotective actions against various stresses and diseases. HN has been shown to induce the phosphorylation of AMP-activated protein kinase (AMPK), which is a negative regulator of receptor activator of nuclear factor-¥êB ligand (RANKL). However, the role of HN in osteoclastogenesis or other skeletal disorders remains unknown. Here, we examined whether HN regulates osteoclastogenesis via AMPK activation using bone marrow-derived macrophage (BMM) cultures. Our results show that HN inhibited RANKL-induced osteoclast formation and reduced the expression of genes involved in osteoclastogenesis, including nuclear factor of activated T-cells cytoplasmic 1, osteoclast-associated receptor, cathepsin K, and tartrate-resistant acid phosphatase. Moreover, HN increased the levels of phosphorylated AMPK protein; compound C, an AMPK inhibitor, recovered HN-induced osteoclast differentiation. In addition, we found that HN significantly decreased the levels of RANKL-induced reactive oxygen species in BMMs. Therefore, these results indicate that HN plays an important role in osteoclastogenesis and may function as an inhibitor of bone disorders via AMPK activation.
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KEYWORD
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AMP-activated protein kinase, Humanin, Osteoclastogenesis, Receptor activator of nuclear factor-¥êB, ligand
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