Bimodal actions of reactive oxygen species in the differentiation and bone-resorbing functions of osteoclasts |
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Authors: | Kim Hyunsoo Kim Ick Young Lee Soo Young Jeong Daewon |
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Affiliation: | Division of Molecular Life Sciences and the Center for Cell Signaling Research, Ewha Womans University, Room# 310, Science Building C, Seodaemun-gu Daehyun-dong 11-1, Seoul 120-750, Republic of Korea. |
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Abstract: | In order to demonstrate that cellular redox status undergoes decreased reduction during osteoclast differentiation and further decreased reduction during osteoclastic bone resorption, we analyzed gamma-glutamylcysteinyl synthetase activity, a glutathione synthesis rate-limiting enzyme, and total glutathione and thiol groups. Moderate and severe redox shifts towards a more oxidizing environment induced gradual increases and decreases in osteoclastogenesis. Moreover, while severe glutathione depletion inhibited bone resorption, moderate glutathione repletion enhanced bone resorption. In summary, our observations suggest that there is a threshold for redox status, representing biphasic patterns in osteoclast differentiation and function. |
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Keywords: | ROS, reactive oxygen species H2O2, hydrogen peroxide RANKL, receptor activator of NF-κB ligand BMMs, bone marrow-derived monocytes M-CSF, macrophage colony-stimulating factor TRAP(+) MNCs, tartrate-resistant acid phosphatase(+) multi-nucleated cells γ-GCS, γ-glutamylcysteinyl synthetase GSH, glutathione BSO, smallcaps" >l-buthionine-(S,R)-sulfoximine NAC, N-acetylcysteine |
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