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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Autores principales:	Bokyung Sung, Sahdeo Prasad, Vivek R Yadav, Subash C Gupta, Simone Reuter, Norio Yamamoto, Akira Murakami, Bharat B Aggarwal
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2071b5fa832d4673bf4012e1fc9c25ac
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spelling	oai:doaj.org-article:2071b5fa832d4673bf4012e1fc9c25ac2021-11-18T07:45:17ZRANKL signaling and osteoclastogenesis is negatively regulated by cardamonin.1932-620310.1371/journal.pone.0064118https://doaj.org/article/2071b5fa832d4673bf4012e1fc9c25ac2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23691159/?tool=EBIhttps://doaj.org/toc/1932-6203Bone 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.Bokyung SungSahdeo PrasadVivek R YadavSubash C GuptaSimone ReuterNorio YamamotoAkira MurakamiBharat B AggarwalPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64118 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bokyung Sung Sahdeo Prasad Vivek R Yadav Subash C Gupta Simone Reuter Norio Yamamoto Akira Murakami Bharat B Aggarwal 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.
format	article
author	Bokyung Sung Sahdeo Prasad Vivek R Yadav Subash C Gupta Simone Reuter Norio Yamamoto Akira Murakami Bharat B Aggarwal
author_facet	Bokyung Sung Sahdeo Prasad Vivek R Yadav Subash C Gupta Simone Reuter Norio Yamamoto Akira Murakami Bharat B Aggarwal
author_sort	Bokyung Sung
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.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/2071b5fa832d4673bf4012e1fc9c25ac
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RANKL signaling and osteoclastogenesis is negatively regulated by cardamonin.

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