Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 31, Issue 4, Pages 874-880Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2013.1258
Keywords
reactive oxygen species; macrophage colony-stimulating factor; receptor for activation of nuclear factor kappa B; osteoclastic differentiation; nicotinamide adenine dinucleotide phosphate oxidase
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Macrophage colony-stimulating factor (M-CSF) is essential for differentiation from hematopoietic precursor cells into osteoclasts. M-CSF transiently increased the intracellular level of reactive oxygen species (ROS) through an NADPH oxidase (Nox) and induced the expression of receptor for activation of nuclear factor-kappa B (RANK) in early-stage osteoclast precursor cells (c-fms(+)RANK(-)). Blocking of the activity of Nox with diphenylene iodonium inhibited ROS production, activation of extracellular signal-regulated kinase (ERK), and the expression of RANK, PU.1 and MITF. The suppression of Nox2, but not Nox1, expression by RNA interference inhibited ROS production and RANK expression. These results suggested that ROS produced in response to M-CSF via a process mediated by Nox2 acted as an intracellular signaling mediator for RANK expression through the activation of ERK and the expression of PU.1 and MITF in early-stage osteoclast precursor cells.
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