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Int. J. Mol. Sci. 2018, 19(1), 125; https://doi.org/10.3390/ijms19010125

The Effects of Kaempferol-Inhibited Autophagy on Osteoclast Formation

1
Department of Oral and Maxillofacial Surgery, Pusan National University Dental Hospital, 20, Geumo-ro, Mulgeum-eup, Yangsan-si 50612, Gyeongsangnam-do, Korea
2
Department of Oral and Maxillofacial Surgery, Medical center, Dong-A University, 26, Daesingongwon-ro, Seo-gu, Busan 49201, Korea
3
BK21 PLUS Project, School of Dentistry, Pusan National University, Busandaehak-ro, 49, Mulguem-eup, Yangsan-si 50612, Gyeongsangnam-do, Korea
4
Department of Oral Anatomy, School of Dentistry, Pusan National University, Busandaehak-ro, 49, Mulguem-eup, Yangsan-si 50612, Gyeongsangnam-do, Korea
Both the authors contributed equally to this study.
*
Author to whom correspondence should be addressed.
Received: 6 November 2017 / Revised: 29 December 2017 / Accepted: 31 December 2017 / Published: 2 January 2018
(This article belongs to the Section Bioactives and Nutraceuticals)
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Abstract

Kaempferol, a flavonoid compound, is derived from the rhizome of Kaempferia galanga L., which is used in traditional medicine in Asia. Autophagy has pleiotropic functions that are involved in cell growth, survival, nutrient supply under starvation, defense against pathogens, and antigen presentation. There are many studies dealing with the inhibitory effects of natural flavonoids in bone resorption. However, no studies have explained the relationship between the autophagic and inhibitory processes of osteoclastogenesis by natural flavonoids. The present study was undertaken to investigate the inhibitory effects of osteoclastogenesis through the autophagy inhibition process stimulated by kaempferol in murin macrophage (RAW 264.7) cells. The cytotoxic effect of Kaempferol was investigated by MTT assay. The osteoclast differentiation and autophagic process were confirmed via tartrate-resistant acid phosphatase (TRAP) staining, pit formation assay, western blot, and real-time PCR. Kaempferol controlled the expression of autophagy-related factors and in particular, it strongly inhibited the expression of p62/SQSTM1. In the western blot and real time-PCR analysis, when autophagy was suppressed with the application of 3-Methyladenine (3-MA) only, osteoclast and apoptosis related factors were not significantly affected. However, we found that after cells were treated with kaempferol, these factors inhibited autophagy and activated apoptosis. Therefore, we presume that kaempferol-inhibited autophagy activated apoptosis by degradation of p62/SQSTM1. Further study of the p62/SQSTM1 gene as a target in the autophagy mechanism, may help to delineate the potential role of kaempferol in the treatment of bone metabolism disorders. View Full-Text
Keywords: bone remodeling; osteoporosis; bisphosphonate-related osteonecrosis of the jaw (BRONJ); osteoclast differentiation; autophagy; flavonoids bone remodeling; osteoporosis; bisphosphonate-related osteonecrosis of the jaw (BRONJ); osteoclast differentiation; autophagy; flavonoids
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kim, C.-J.; Shin, S.-H.; Kim, B.-J.; Kim, C.-H.; Kim, J.-H.; Kang, H.-M.; Park, B.-S.; Kim, I.-R. The Effects of Kaempferol-Inhibited Autophagy on Osteoclast Formation. Int. J. Mol. Sci. 2018, 19, 125.

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