Cadmium-induced decrease in RUNX2 mRNA expression and recovery by the antioxidant N-acetylcysteine (NAC) in the human osteoblast-like cell line, Saos-2.
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 microM 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 microM CdCl2. Pretreatment with the antioxidant NAC (1mM) 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.
Smith
Spenser S
SS
Department of Biology, The College of Idaho, 2112 Cleveland Blvd., Caldwell, ID 83605, USA.
Reyes
Jackeline Rodriguez
JR
Arbon
Kate S
KS
Harvey
Wendy A
WA
Hunt
Lindsey M
LM
Heggland
Sara J
SJ
D000111:Acetylcysteine / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019256:Cadmium Chloride / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004785:Environmental Pollutants / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D004785:Environmental Pollutants; D016166:Free Radical Scavengers; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D017382:Reactive Oxygen Species; D005978:Glutathione; D019256:Cadmium Chloride; D000111:Acetylcysteine