Effect of cadmium on osteogenesis within diffusion chambers by bone marrow cells: biochemical evidence of decreased bone formation capacity

Abstract

The biological and biochemical effects of cadmium administration on bone marrow in rats were examined. When young adult rats were administered cadmium (Cd) repeatedly at a dose of 750 micrograms/kg body wt for up to 4 weeks, metallothionein mRNA was detected by a gene expression analysis in their bone marrow at 2 weeks after the first Cd administration, though the amounts were lower than those in liver. To determine the direct effect of cadmium on bone formation, the potential of Cd-treated bone marrow cells and demineralized bone matrix (DBM) to form bone and cartilage was assessed using a diffusion chamber (DC) in vivo, by histological examination, and by biochemical parameters such as alkaline phosphatase (ALP) activity, total calcium and phosphorus content, and the bone-specific vitamin K-dependent Gla-containing protein (BGP) content, relative to mineralization. Diffusion chambers were inoculated with DBM and bone marrow cells from either Cd-treated or nontreated rats (control) and were then implanted subcutaneously into syngeneic nontreated rats. The accumulation of BGP in DCs with Cd-treated bone marrow was significantly lower than that in control DCs. Unlike in control DC, a peak of ALP activity did not occur at 4 weeks postimplantation in DC implants inoculated with Cd-treated bone marrow; the ALP activity and calcium content in these implants were also significantly lower than those of the control bone marrow-containing chambers at the early stage of implantation. Histological examinations of chambers with Cd-treated marrow showed a decreased area of cartilage and bone foci compared with those in control chambers. These findings suggest that Cd administration inhibits the osteoblastic and chondroblastic differentiation pathway in bone marrow through direct effects on these cells.