Effects of sub-toxic Cadmium concentrations on bone gene expression program: results of an in vitro study.
Since occupational and environmental exposure to the heavy metal Cadmium (Cd) affects human health this study investigated the effects of exposure to a single, or multiple, sub-toxic Cd concentrations on sub-confluent and confluent human osteoblast growth and expression of specific bone differentiation markers. RT-PCR quantified gene expression of type I collagen, metalloprotease (MMP13), runt-related transcription factor-2 (RUNX2), osterix, osteocalcin, osteonectin, alkaline phosphatase, integrins and bone sialoprotein (BSP). Expression of fibroblast growth factors 1 and 2 (FGF1, FGF2), transforming growth factor-beta(3) (TGFbeta(3)) and bone morphogenetic protein-2 (BMP2) were also evaluated to determine whether Cd-related effects were mediated by an imbalance in expression. Depending on osteoblast concentration and maturation stages, Cd inhibited or stimulated cell growth, decreased type I collagen, increased MMP13, FGF1 and BMP2 gene expression and stimulated the mineralization process only in continuously exposed cultures. These results suggest that in vivo, acute or chronic exposure to sub-toxic Cd concentrations may affect bone formation differently and support the hypothesis that Cd-induced bone disorders may involve downstream changes in growth factor expression. The results are of interest in forensic and occupational medicine in establishing preventive measures to reduce professional exposure risks.
Bodo
Maria
M
Department of Experimental Medicine and Biochemistry, University of Perugia, Perugia, Italy. bodo@unipg.it
Balloni
Stefania
S
Lumare
Eleonora
E
Bacci
Mauro
M
Calvitti
Mario
M
Dell'Omo
Marco
M
Murgia
Nicola
N
Marinucci
Lorella
L
D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001846:Bone Development / Q000187:drug effects* / Q000235:genetics; D001842:Bone and Bones / Q000187:drug effects*; D019256:Cadmium Chloride / Q000633:toxicity*; D002113:Calcification, Physiologic / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D015415:Biomarkers; D004785:Environmental Pollutants; D016326:Extracellular Matrix Proteins; D011506:Proteins; D012333:RNA, Messenger; D000469:Alkaline Phosphatase; D019256:Cadmium Chloride