実験的骨形成モデルを用いた初期の骨形成に及ぼすカドミウムの影響 ： アルカリフォスファターゼ，カルシウム，燐，およびオステオカルシンmRNAの動態

Abstract

To determine the direct effect of cadmium (Cd) 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 measurement of biochemical parameters such as alkaline phosphatase (ALP) activity, total calcium and phosphorus contents, the bone-specific protein, osteocalcin content, and by the gene expression of osteopontin and osteocalcin. Diffusion chambers were inoculated with DBM and bone marrow cells from either Cd-treated or non-treated rats (control) and were then implanted subcutaneously into syngeneic non-treated rats. Unlikely in control DC, a peak of ALP activity did not occur at 4 weeks postimplantation in DC implants inoculated with Cd-treated bone marrow. ALP activity, and calcium and phosphorus contents in these Cd-treated DC implants were significantly lower than those of the control DCs at the early stage of implantation. The accumulation of osteocalcin in DCs with Cd-treated bone marrow was also significantly lower than that in control DCs. By gene expression analyses, osteopontin mRNA was intensly expressed in the DC with control and followed with Cd-treated bone marrow DC 5 weeks after implantation. On the contrary, the expression of osteocalcin mRNA in the DCs with Cd-treated bone marrow was much lower than that in control DCs by both Northern blot analysis and also in situ hybridization. These results indicate that Cd administration restrains the osteoblastic differentiation pathway in bone marrow through direct effects on these cells.