title: Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation.
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 RANKL-induced 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. [BMB Reports 2017; 50(2): 103-108].
authors.affiliation: Departments of Molecular and Cellular Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Bak
authors.affiliation: Departments of Molecular and Cellular Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Suji
authors.initials: S
authors.lastname: Kim
authors.affiliation: Departments of Molecular and Cellular Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Hae-Jun
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Departments of Molecular and Cellular Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Jung-A
authors.initials: JA
authors.lastname: Yun
authors.affiliation: Departments of Molecular and Cellular Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Wan-Sung
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Departments of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Department of Anesthesiology and Pain Medicine, Hanyang University Hospital, Seoul 04763, Korea.
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Departments of Molecular and Cellular Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Kwon-Soo
authors.initials: KS
authors.lastname: Ha
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea.
authors.forename: Young-Guen
authors.initials: YG
authors.lastname: Kwon
authors.affiliation: Departments of Molecular and Cellular Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000517:prevention & control; D002248:Carbon Monoxide / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D053245:RANK Ligand / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D053245:RANK Ligand; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1