Bimodal actions of reactive oxygen species in the differentiation and bone-resorbing functions of osteoclasts.
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.
Kim
Hyunsoo
H
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.
Kim
Ick Young
IY
Lee
Soo Young
SY
Jeong
Daewon
D
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D008264:Macrophages / Q000166:cytology; D051379:Mice; D009000:Monocytes / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species