Ethanol inhibits human osteoblastic cell proliferation.
The habitual consumption of alcoholic beverages is clearly associated with low bone mass and an increased prevalence of skeletal fractures. Microscopic analysis of skeletal tissue from alcoholic patients reveals reduced osteoblast number and suppressed bone formation activity with a relative sparing of resorptive indices. The decreased number of osteoblasts observed in alcoholic subjects results from either impaired proliferation or accelerated senescence. Polyamines and ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine synthesis, are essential for cell proliferation in a variety of cell types. To determine if the adverse effect of ethanol on osteoblast number involves modulation of polyamine biosynthesis, we examined the effect of ethanol on parameters of cell growth and ODC activity in a human osteoblast-like osteosarcoma cell line (TE-85). Ethanol markedly impaired DNA synthesis and cell proliferation in a dose-dependent fashion, but alkaline phosphatase activity (a marker of differentiated osteoblast function) remained intact, and accelerated apoptosis was not evident. Thus, the reduced osteoblastic cell number was a result of a direct effect on proliferative processes rather than a nonspecific toxic effect of ethanol to accelerate cell death. Induction of ODC activity was impaired in ethanol-exposed cell cultures in a dose-dependent fashion that paralleled the antiproliferative effects. Finally, supplemental polyamine administration substantially improved DNA synthesis in ethanol-exposed UMR 106-01 cell cultures. These data confirm a direct inhibitory effect of ethanol on osteoblast proliferation without overt cellular toxicity that may, in part, explain the reduced bone mass observed in those who consume excessive amounts of alcohol.
Klein
R F
RF
Bone and Mineral Research Unit, Veterans Affairs Medical Center, Portland, OR 97207, USA.
Fausti
K A
KA
Carlos
A S
AS
D015519:Bone Density / Q000187:drug effects; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D065108:Ornithine Decarboxylase Inhibitors; D010006:Osteoblasts / Q000187:drug effects*; D011073:Polyamines / Q000378:metabolism; D014407:Tumor Cells, Cultured
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D000431:Ethanol