A study on the mechanism of bone lesion by cadmium Effect of cadmium on the bone formation in cultured MC3T3-E1

Research Project

Project/Area Number	63570241
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Hygiene
Research Institution	Nara medical University
Principal Investigator	MORIYAMA T. Nara medical university, professor, 医学部, 教授 (60075041)
Co-Investigator(Kenkyū-buntansha)	OGOSHI K. Nara medical university, assistant researcher, 医学部, 助手 (20106503) DOHI Y. Nara medical university, assistant professor, 医学部, 助教授 (50155628)
Project Period (FY)	1988 – 1989
Project Status	Completed (Fiscal Year 1989)
Budget Amount *help	¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Keywords	Cadmium / bone lesion / bone formation / osteoblast / MC3T3-E1 / 石灰化
Research Abstract	To obtain further information on the mechanism of bone damage caused by cadmium(Cd), the effect of Cd on the differentiation of bone cells (MC3T3-E1) were examined by quantitating DNA synthesis, alkaline phosphatase(ALP) activity and collagen synthesis. After cells were cultured for 3 days, metal ions were added to the medium containing 10% fetal bovine serum and cells were subsequently cultured for 7 days at 37ﾟC in 5% CO_2 in air. Although 10^<-8>M of Cd have no significant influence on ALP activity of the cells, 10^<-7>M and 10^<-6>M of Cd decreased ALP activity by 25% and 30% of control value. 10^<-5>M Cd remarkably decreased ALP activity. DNA content and hydroxyproline content were also decreased by exposure to 10^<-5>M of Cd, less than 10^<-6>M Cd didn't affect both the parameters. Since there are some reports that zine(Zn) has a protective effect against the toxicity of Cd, we also examined the effect of Zn coexisting with Cd on MC3T3-E1. Interestingly, morphological changes by 10^<-5>M of Cd were improved by 10^<-4>M of Zn. ALP activity, protein content, and hydroxyproline content decreased by exposure to 10^<-5>M of Cd were also recovered by the addition of 10^<-4>M Zn to the culture medium. The present study suggests that ALP molecule, sythesized in osteoblastic cells and bound to cell membrane, may be the primary target of Cd. The inactivated ALP by exposure to low concentration of Cd for a long period may affect the function of osteoblastic cells in bone.