Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Role of mitochondrial reactive oxygen species in osteoclast differentiation. Ann N Y Acad Sci 2010 Mar;1192(1):245-52

Date

04/16/2010

Pubmed ID

20392243

Pubmed Central ID

PMC2856121

DOI

10.1111/j.1749-6632.2009.05377.x

Scopus ID

2-s2.0-77950686292 (requires institutional sign-in at Scopus site)   105 Citations

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.

Author List

Srinivasan S, Koenigstein A, Joseph J, Sun L, Kalyanaraman B, Zaidi M, Avadhani NG

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Acid Phosphatase
Animals
Antioxidants
Calcineurin
Cell Differentiation
Cell Hypoxia
Cells, Cultured
Isoenzymes
Membrane Potential, Mitochondrial
Mice
Mitochondria
NF-kappa B
Organophosphorus Compounds
Osteoclasts
Reactive Oxygen Species
Tartrate-Resistant Acid Phosphatase
Ubiquinone