Stimulatory effect of ?-alanyl-L-histidinato zinc on cell proliferation is dependent on protein synthesis in osteoblastic MC3T3-E1 cells

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Abstract
The effect of β-alanyl-L-histidinato zinc (AHZ) on bone metabolism was investigated in osteoblastic MC3T3-El cells. Cells were cultured for 3 days at 37°C in a CO2 incubator in plastic dishes containing α-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 (10−7–10−5M) stimulated the proliferation of cells. AHZ (10−6 and 10−5M) increased deoxyribonucleic acid (DNA) content in the cells with 48hr-culture. This increase was completely blocked by the presence of cycloheximide (10−6M) or hydroxyurea (10−3M). Also, the presence of cycloheximide (10−6M) completely inhibited the AHZ (10−5M)-induced increase in the proliferation of cells. Meanwhile, parathyroid hormone (10−7M), estrogen (10−9M) and insulin (10−M) significantly increased cellular DNA content. However, these hormonal effects clearly lowered in comparison with that of AHZ (10−5M). Dibutyryl cyclic AMP (10−4M) and zinc sulfate (10−5M) 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 cellsin vitro and that this effect is dependent on protein synthesis.