title: Role of mitochondrial reactive oxygen species in osteoclast differentiation.
abstract: Previously we showed that hypoxia-induced mitochondrial respiratory stress in RAW 264.7 macrophages and other cells caused activation of retrograde signaling (also known as mitochondrial respiratory stress signaling) and the appearance of tartrate-resistant acid phosphatase (TRAP)-positive cells. In the present study, we used N-acetyl cysteine and ascorbate (general antioxidants) and MitoQ, a mitochondria-specific antioxidant, to investigate the role of intracellular reactive oxygen species (ROS) in osteoclast differentiation. Our results show that hypoxia-mediated mitochondrial dysfunction, as tested by disruption of mitochondrial transmembrane potential, was suppressed by MitoQ as well as by the other antioxidants. These agents also suppressed the activation of mitochondrial retrograde signaling. Interestingly, in terms of molar concentrations, MitoQ was more than 1000-fold more effective than general antioxidants in suppressing the receptor activator of nuclear factor-B ligand-induced differentiation of RAW 264.7 cells into multinucleated and TRAP-positive osteoclasts. We propose that mitochondrial function and intramitochondrial ROS play important roles in osteoclastogenesis.
authors.affiliation: Department of Animal Biology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Satish
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Alexander
authors.initials: A
authors.lastname: Koenigstein
authors.forename: Joy
authors.initials: J
authors.lastname: Joseph
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: B
authors.initials: B
authors.lastname: Kalyanaraman
authors.forename: Mone
authors.initials: M
authors.lastname: Zaidi
authors.forename: Narayan G
authors.initials: NG
authors.lastname: Avadhani
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019703:Calcineurin / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D007527:Isoenzymes / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*; D000071681:Tartrate-Resistant Acid Phosphatase; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D007527:Isoenzymes; D016328:NF-kappa B; D009943:Organophosphorus Compounds; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C429014:mitoquinone; D019703:Calcineurin; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
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