Journal
TOXICOLOGY IN VITRO
Volume 23, Issue 1, Pages 60-66Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2008.10.011
Keywords
Cadmium; RUNX2; Antioxidant; Osteoblast; Osteoporosis
Categories
Funding
- NIH [P20RR016454]
- National Institute of Environmental Health Sciences [NIH R15ES015866]
- Sigma Xi Scientific Research Society
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Exposure to cadmium poses a threat to human health, including increased Susceptibility to developing the bone disease osteoporosis. Despite its recognized importance as an environmental toxin, little is known about how cadmium directly impacts bone-forming osteoblasts. We previously reported that cadmium induces apoptosis in human osteoblast-like Saos-2 cells. In this work, we hypothesize that cadmium exposure induces oxidative stress which leads to decreased RUNX2 mRNA expression and increased apoptotic death, and predict that the antioxidant NAC mitigates the damaging effects of cadmium. Oxidative stress is implicated in osteoporosis; furthermore the osteoblast transcriptional factor RUNX2 is reported to play a protective role against osteoporosis in postmenopausal women. Cells treated With 10 mu M CdCl2 exhibited signs of oxidative damage including depletion in glutathione, increased reactive oxygen species formation, and enhanced lipid peroxidation. RUNX2 mRNA expression, by RT-PCR, Was Significantly reduced after exposure to 10 mu M CdCl2. Pretreatment with the antioxidant NAC (1 mM) prevented cadmium-induced decrease in RUNX2 mRNA and protected cells from apoptotic death. This Study provides insight into the mechanisms underlying cadmium-induced osteotoxicity. In addition, this study distinguishes itself by identifying RUNX2 as a target for heavy metal-induced osteotoxicity. (C) 2008 Elsevier Ltd. All rights reserved.
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