Cadmium Induces Apoptosis in the Human Osteoblast-like Cell Line Saos-2

Abstract

Human exposure to the heavy metal cadmium has been associated with the development of bone diseases, including osteoporosis and osteomalacia. The mechanisms by which cadmium exerts a direct effect on bone remain unclear. Bone cells go through apoptosis for proper bone remodeling; therefore, it was hypothesized that cadmium disrupts this normal balance by inducing apoptosis. Human osteoblast-like cells (Saos-2) were treated with 10-200 muM cadmium chloride (CdCl2) and evaluated by trypan blue staining and phase-contrast microscopy. Exposure to CdCl2 resulted in decreased cell viability and changes in cell morphology characteristic of apoptosis. The role of apoptosis in cadmium-induced toxicity was further evaluated using the fluorescent marker annexin V, which detects externalization of cell membrane phosphatidylserine. Nuclear changes associated with apoptosis were assessed by Hoechst staining and a DNA fragmentation assay. A significant increase in annexin V-positive cells was observed following CdCl2 treatment. Nuclear changes associated with apoptosis, including marginalization and condensing of chromatin and DNA fragmentation, were also observed following CdCl2 treatment. Cadmium-induced apoptosis in Saos-2 cells was also accompanied by an increase in caspase-3 activity. The addition of the caspase-3 inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) or the known cadmium chelating agent potassium bis(2-hydroxyethy)dithiocarbamate, (K[bhedtc]), blocked caspase-3 activation induced by cadmium. Collectively, this study has identified a role for apoptosis in cadmium-induced toxicity in bone cells, and provides insight for future studies on mechanisms underlying the disruption of apoptotic signaling cascades in bone and the relationship to bone disease.

Hg2+ and Cd2+ interact differently with biomimetic erythrocyte membranes

“…has been previously shown to interact with lipids similarly to Ca 2? (Girault et al 1998) and both ions contributed to the externalization of PS in other cell types, inducing apoptosis (Watjen et al 2002;Coonse et al 2007;Lee et al 2007;Sarang et al 2007). In contrast to our Hg 2?…”

Relationship between environmental exposure to cadmium and bone metabolism in a non-polluted area of Japan

“…We mainly investigated the relationships between cadmium-associated biomarkers and bone metabolic markers, as well as ultrasonic bone evaluation parameters, because previous studies reported that bone absorption was accelerated by cadmium intake. The other parameters will be investigated in a further study [31][32][33][34][35][36][37][38][39][40][41][42]. Correlation between two substances in urine was calculated from the original measured values, adjusted by age and logarithmic transformed creatinine, while correlations between substances in urine and other parameters were calculated from values in urine corrected by urinary creatinine adjusted by age [43].…”

“…A decrease in bone mineral density and inhibition of bone formation before the manifestation of renal dysfunction was reported in experimental animals [36]. Furthermore, Coonse and colleagues [37] reported that cadmium induced apoptosis in the cultured osteoblast-like cell line Saos-2. Thus, the possibility of a direct effect of cadmium on bone has been suggested [38].…”

Ailing bones and failing kidneys: a case of chronic cadmium toxicity

“…Cadmium also interacts with renal mitochondrial hydroxylases of the vitamin D 3 endocrine complex, thereby contributing to skeletal injury. 5,6 Coonse et al 7 reported that cadmium induces apoptosis in the cultured osteoblast-like cell line Saos-2. Thus, there is a possibility of a direct effect of cadmium on bone health.…”