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Mechanism of Zn2+-induced stimulation and Cd2+-induced inhibition of bone nodule (BN) formation was studied in calvarial osteoblastic cells isolated from rats of various ages. Zn2+ dose-dependently increased BN formation at 10-8м or higher concentrations in the cells from 10-week-old (young) and 90-week-old (aged) rats and the degree of stimulation was much smaller in the aged rat cells. Conversely, Cd2+ dose-depedently inhibited BN formation in the young and aged rat cells, with the effect being more prominent in the aged rat cells. The lowest concentrations required to reduce the area of BN in the young and aged rat cells were 10-8 and 10-9м, respectively. Insulin-like growth factor (IGF)-I (10-6м) increased the area of BN by 350% and 50% in the young and aged rat cells, respectively. Zn2+ (3×10-6м) stimulated IGF-I production by 580% and 100% in the young and aged rat cells, respectively. Anti-IGF-I antibody almost completely inhibited the stimulatory effect of Zn2+ on BN formation in the young and aged rat cells. These results indicate that the effect of Zn2+ is mediated through the production of IGF-I. The stimulation of IGF-I production by Zn2+ (3×10-6м) was blocked by Cd2+ (10-7м) in the young and aged rat cells. Cd2+ (10-7м) also inhibited the increase in BN formation by IGF-I in the aged, but not in the young rat cells. These results indicate that Cd2+ inhibits the induction of IGF-I production by Zn2+ and the subsequent action of IGF-I on osteoblasts in the aged rat cells, while only the IGF-I production is affected in the young rat cells.

Age-Dependent Changes in the Effect of Zinc and Cadmium on Bone Nodule Formation in Rat Calvarial Osteoblasts.