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

Sun Uk Bak, Suji Kim, Hae Jun Hwang, Jung A. Yun, Wan Sung Kim, Moo Ho Won, Ji Yoon Kim, Kwon Soo Ha, Young-Guen Kwon, Young Myeong Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced 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.

Original languageEnglish
Pages (from-to)103-108
Number of pages6
JournalBMB reports
Volume50
Issue number2
DOIs
Publication statusPublished - 2017 Jan 1

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Heme Oxygenase-1
Carbon Monoxide
Osteogenesis
Oxidation-Reduction
Chemical activation
Macrophages
Heme
Bilirubin
Iron
Biliverdine
Heme Oxygenase (Decyclizing)
Hemin
Osteoclasts
Reactive Oxygen Species
Bone
Ligands
Degradation
Bone Marrow
tricarbonyldichlororuthenium (II) dimer
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

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. In: BMB reports. 2017 ; Vol. 50, No. 2. pp. 103-108.
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abstract = "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 RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced 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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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.

In: BMB reports, Vol. 50, No. 2, 01.01.2017, p. 103-108.

Research output: Contribution to journalArticle

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