Hemeoxygenase-1 maintains bone mass via attenuating a redox imbalance in osteoclast. (5th July 2015)

• Record Type: Journal Article
• Authors: Ke, Ke; Safder, M.A.; Sul, Ok-Joo; Kim, Woon-Ki; Suh, Jae-Hee; Joe, Yeonsoo; Chung, Hun-Taeg; Choi, Hye-Seon
• Is Part Of: Molecular and cellular endocrinology. Volume 409(2015)
• Page Start: 11
• Page End: 20
• Publication Date: 2015-07-05
• Subjects: BMD bone mineral density -- BMM bone marrow-derived macrophage -- CO carbon monoxide -- CORM2 CO-releasing molecule 2 -- CTX-1 C-telopeptide fragments of collagen type 1 -- DPI diphenyliodonium -- H2DCFH-DA 2′, 7 ′-dichlorofluorescein diacetate -- EMSA electrophoretic mobility shift assay -- HO-1 heme oxygenase-1 -- KO knockout -- M-CSF macrophage-colony stimulating factor -- MNC multinucleated cells -- NADPH oxidase nicotinamide adenine dinucleotide phosphate oxidase -- NAC N-acetylcysteine -- NF-κB nuclear factor-κB -- NFAT2 nuclear factor of activated T cells, cytoplasmic 1 -- OC osteoclast -- OVX ovariectomy -- PINP N-terminal propeptide of type I procollagen -- qPCR quantitative PCR -- RANKL receptor activator of nuclear factor-κB ligand -- ROS reactive oxygen species -- siRNA small interfering RNA -- scRNA scrambled siRNA -- TRAP tartrate-resistant acid phosphatase -- µCT micro CT; Heme oxygenase-1 -- Reactive oxygen species -- Osteoclast -- Receptor activator of nuclear factor-κB ligand signaling; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.03.022
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlight: We have demonstrated the potential role of heme oxygenase-1 in maintaining bone mass by negatively regulating osteoclasts. Graphical Abstract: 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.