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Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL)....

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Autores principales: Bak, Sun-Uk, Kim, Suji, Hwang, Hae-Jun, Yun, Jung-A, Kim, Wan-Sung, Won, Moo-Ho, Kim, Ji-Yoon, Ha, Kwon-Soo, Kwon, Young-Guen, Kim, Young-Myeong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342874/
https://www.ncbi.nlm.nih.gov/pubmed/28088947
http://dx.doi.org/10.5483/BMBRep.2017.50.2.220
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author Bak, Sun-Uk
Kim, Suji
Hwang, Hae-Jun
Yun, Jung-A
Kim, Wan-Sung
Won, Moo-Ho
Kim, Ji-Yoon
Ha, Kwon-Soo
Kwon, Young-Guen
Kim, Young-Myeong
author_facet Bak, Sun-Uk
Kim, Suji
Hwang, Hae-Jun
Yun, Jung-A
Kim, Wan-Sung
Won, Moo-Ho
Kim, Ji-Yoon
Ha, Kwon-Soo
Kwon, Young-Guen
Kim, Young-Myeong
author_sort Bak, Sun-Uk
collection PubMed
description Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKL-induced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKL-induced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1(+/−) cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation.
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spelling pubmed-53428742017-04-20 Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation Bak, Sun-Uk Kim, Suji Hwang, Hae-Jun Yun, Jung-A Kim, Wan-Sung Won, Moo-Ho Kim, Ji-Yoon Ha, Kwon-Soo Kwon, Young-Guen Kim, Young-Myeong BMB Rep Articles Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKL-induced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKL-induced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1(+/−) cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. Korean Society for Biochemistry and Molecular Biology 2017 2017-02-28 /pmc/articles/PMC5342874/ /pubmed/28088947 http://dx.doi.org/10.5483/BMBRep.2017.50.2.220 Text en Copyright © 2017 by the The Korean Society for Biochemistry and Molecular Biology http://creativecommons.org/licenses/by-nc/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Bak, Sun-Uk
Kim, Suji
Hwang, Hae-Jun
Yun, Jung-A
Kim, Wan-Sung
Won, Moo-Ho
Kim, Ji-Yoon
Ha, Kwon-Soo
Kwon, Young-Guen
Kim, Young-Myeong
Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation
title Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation
title_full Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation
title_fullStr Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation
title_full_unstemmed Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation
title_short Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation
title_sort heme oxygenase-1 (ho-1)/carbon monoxide (co) axis suppresses rankl-induced osteoclastic differentiation by inhibiting redox-sensitive nf-κb activation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342874/
https://www.ncbi.nlm.nih.gov/pubmed/28088947
http://dx.doi.org/10.5483/BMBRep.2017.50.2.220
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