RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin

Bone loss/resorption or osteoporosis is a disease that is accelerated with aging and age-associated chronic diseases such as cancer. Bone loss has been linked with human multiple myeloma, breast cancer, and prostate cancer and is usually treated with bisphosphonates, and recently approved denosumab,...

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Main Authors:	Sung, Bokyung, Prasad, Sahdeo, Yadav, Vivek R., Gupta, Subash C., Reuter, Simone, Yamamoto, Norio, Murakami, Akira, Aggarwal, Bharat B.
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656934/

id	pubmed-3656934
recordtype	oai_dc
spelling	pubmed-36569342013-05-20 RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin Sung, Bokyung Prasad, Sahdeo Yadav, Vivek R. Gupta, Subash C. Reuter, Simone Yamamoto, Norio Murakami, Akira Aggarwal, Bharat B. Research Article Bone loss/resorption or osteoporosis is a disease that is accelerated with aging and age-associated chronic diseases such as cancer. Bone loss has been linked with human multiple myeloma, breast cancer, and prostate cancer and is usually treated with bisphosphonates, and recently approved denosumab, an antibody against receptor activator of NF-κB ligand (RANKL). Because of the numerous side effects of the currently available drugs, the search continues for safe and effective therapies for bone loss. RANKL, a member of the TNF superfamily, has emerged as a major mediator of bone loss via activation of osteoclastogenesis. We have identified cardamonin, a chalcone isolated from Alpinia katsumadai Hayata that can affect osteoclastogenesis through modulation of RANKL. We found that treatment of monocytes with cardamonin suppressed RANKL-induced NF-κB activation and this suppression correlated with inhibition of IκBα kinase and of phosphorylation and degradation of IκBα, an inhibitor of NF-κB. Furthermore, cardamonin also downregulated RANKL-induced phosphorylation of MAPK including ERK and p38 MAPK. Cardamonin suppressed the RANKL-induced differentiation of monocytes to osteoclasts in a dose-dependent and time-dependent manner. We also found that an inhibitor of NF-κB essential modulator (NEMO) blocked RANKL-induced osteoclastogenesis, indicating a direct link with NF-κB. Finally, osteoclastogenesis induced by human breast cancer cells or human multiple myeloma cells were completely suppressed by cardamonin. Collectively, our results indicate that cardamonin suppresses osteoclastogenesis induced by RANKL and tumor cells by suppressing activation of the NF-κB and MAPK pathway. Public Library of Science 2013-05-17 /pmc/articles/PMC3656934/ /pubmed/23691159 http://dx.doi.org/10.1371/journal.pone.0064118 Text en © 2013 Sung et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sung, Bokyung Prasad, Sahdeo Yadav, Vivek R. Gupta, Subash C. Reuter, Simone Yamamoto, Norio Murakami, Akira Aggarwal, Bharat B.
spellingShingle	Sung, Bokyung Prasad, Sahdeo Yadav, Vivek R. Gupta, Subash C. Reuter, Simone Yamamoto, Norio Murakami, Akira Aggarwal, Bharat B. RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin
author_facet	Sung, Bokyung Prasad, Sahdeo Yadav, Vivek R. Gupta, Subash C. Reuter, Simone Yamamoto, Norio Murakami, Akira Aggarwal, Bharat B.
author_sort	Sung, Bokyung
title	RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin
title_short	RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin
title_full	RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin
title_fullStr	RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin
title_full_unstemmed	RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin
title_sort	rankl signaling and osteoclastogenesis is negatively regulated by cardamonin
description	Bone loss/resorption or osteoporosis is a disease that is accelerated with aging and age-associated chronic diseases such as cancer. Bone loss has been linked with human multiple myeloma, breast cancer, and prostate cancer and is usually treated with bisphosphonates, and recently approved denosumab, an antibody against receptor activator of NF-κB ligand (RANKL). Because of the numerous side effects of the currently available drugs, the search continues for safe and effective therapies for bone loss. RANKL, a member of the TNF superfamily, has emerged as a major mediator of bone loss via activation of osteoclastogenesis. We have identified cardamonin, a chalcone isolated from Alpinia katsumadai Hayata that can affect osteoclastogenesis through modulation of RANKL. We found that treatment of monocytes with cardamonin suppressed RANKL-induced NF-κB activation and this suppression correlated with inhibition of IκBα kinase and of phosphorylation and degradation of IκBα, an inhibitor of NF-κB. Furthermore, cardamonin also downregulated RANKL-induced phosphorylation of MAPK including ERK and p38 MAPK. Cardamonin suppressed the RANKL-induced differentiation of monocytes to osteoclasts in a dose-dependent and time-dependent manner. We also found that an inhibitor of NF-κB essential modulator (NEMO) blocked RANKL-induced osteoclastogenesis, indicating a direct link with NF-κB. Finally, osteoclastogenesis induced by human breast cancer cells or human multiple myeloma cells were completely suppressed by cardamonin. Collectively, our results indicate that cardamonin suppresses osteoclastogenesis induced by RANKL and tumor cells by suppressing activation of the NF-κB and MAPK pathway.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656934/
_version_	1611978728085127168

RANKL Signaling and Osteoclastogenesis Is Negatively Regulated by Cardamonin

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