title: Hemeoxygenase-1 maintains bone mass via attenuating a redox imbalance in osteoclast.
abstract: Heme oxygenase-1 (HO-1) has long been considered to be an endogenous antioxidant. However, the role of HO-1 is highly controversial in developing metabolic diseases. We hypothesized that HO-1 plays a role in maintaining bone mass by alleviating a redox imbalance. We investigated its role in bone remodeling. The absence of HO-1 in mice led to decreased bone mass with elevated activity and number of OCs, as well as higher serum levels of reactive oxygen species (ROS). HO-1, which is constitutively expressed at a high level in osteoclast (OC) precursors, was down-regulated during OC differentiation. HO-1 deficiency in bone marrow macrophages (BMM) in vitro resulted in increased numbers and activity of OCs due to enhanced receptor activator of nuclear factor-κB ligand (RANKL) signaling. This was associated with increased activation of nuclear factor-κB and of nuclear factor of activated T-cells, cytoplasmic 1 along with elevated levels of intracellular calcium and ROS. Decreased bone mass in the absence of HO-1 appears to be mainly due to increased osteoclastogenesis and bone resorption resulting from elevated RANKL signaling in OCs. Our data highlight the potential role of HO-1 in maintaining bone mass by negatively regulating OCs.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Ke
authors.initials: K
authors.lastname: Ke
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: M A
authors.initials: MA
authors.lastname: Safder
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Ok-Joo
authors.initials: OJ
authors.lastname: Sul
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Woon-Ki
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Department of Pathology, Ulsan University Hospital, Ulsan 682-714, Republic of Korea.
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Suh
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea. Electronic address: hschoi@mail.ulsan.ac.kr.
authors.forename: Hye-Seon
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D001862:Bone Resorption; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000172:deficiency / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D010010:Osteoclasts / Q000502:physiology*; D010084:Oxidation-Reduction; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000097:blood; D015398:Signal Transduction
chemical_list: D008565:Membrane Proteins; D053245:RANK Ligand; D017382:Reactive Oxygen Species; C505689:Tnfsf11 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Heme oxygenase-1; Osteoclast; Reactive oxygen species; Receptor activator of nuclear factor-κB ligand signaling