Humanin suppresses receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via AMP-activated protein kinase activation
10.4196/kjpp.2019.23.5.411
- Author:
Namju KANG
1
;
Ki Woo KIM
;
Dong Min SHIN
Author Information
1. Department of Oral Biology, BK21 PLUS Project, Yonsei University College of Dentistry, Seoul 03722, Korea. dmshin@yuhs.ac
- Publication Type:Original Article
- Keywords:
AMP-activated protein kinase;
Humanin;
Osteoclastogenesis;
Receptor activator of nuclear factor-κB;
ligand
- MeSH:
Acid Phosphatase;
AMP-Activated Protein Kinases;
Cathepsin K;
Cytoplasm;
Macrophages;
Osteoclasts;
Phosphorylation;
Reactive Oxygen Species;
T-Lymphocytes
- From:The Korean Journal of Physiology and Pharmacology
2019;23(5):411-417
- CountryRepublic of Korea
- Language:English
-
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-κB 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.
