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http://dx.doi.org/10.4196/kjpp.2019.23.5.411

Humanin suppresses receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via AMP-activated protein kinase activation  

Kang, Namju (Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry)
Kim, Ki Woo (Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry)
Shin, Dong Min (Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.23, no.5, 2019 , pp. 411-417 More about this Journal
Abstract
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-${\kappa}B$ 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, osteoclastassociated 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.
Keywords
AMP-activated protein kinase; Humanin; Osteoclastogenesis; Receptor activator of nuclear factor-${\kappa}B$; ligand;
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