Author(s): Hashizume M, Yamaguchi M
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Abstract The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in osteoblastic MC3T3-E1 cells. Cells were cultured for 3 days at 37 degrees C in a CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10\% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1\% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further for appropriate periods of time. The presence of AHZ (10(-7)-10(-5) M) stimulated the proliferation of cells. AHZ (10(-6) and 10(-5) M) increased deoxyribonucleic acid (DNA) content in the cells with 48 hr-culture. This increase was completely blocked by the presence of cycloheximide (10(-6) M) or hydroxyurea (10(-3) M). Also, the presence of cycloheximide (10(-6) M) completely inhibited the AHZ (10(-5) M)-induced increase in the proliferation of cells. Meanwhile, parathyroid hormone (10(-7) M), estrogen (10(-9) M) and insulin (10(-8) M) significantly increased cellular DNA content. However, these hormonal effects clearly lowered in comparison with that of AHZ (10(-5) M). Dibutyryl cyclic AMP (10(-4) M) and zinc sulfate (10(-5) M) did not cause a significant increase in cellular DNA content. The present results support the view that AHZ has a direct specific proliferative effect on osteoblastic cells in vitro and that this effect is dependent on protein synthesis.
This article was published in Mol Cell Biochem
and referenced in Journal of Diabetes & Metabolism