The dose-response effects of ethanol on the human fetal osteoblastic cell line.
Alcohol is a risk factor for the development of osteoporosis, especially in men. Chronic alcohol abuse decreases bone mass, which contributes to the increased incidence of fractures. To better understand the mechanism of action of ethanol on bone metabolism, we have studied the dose-response effects of ethanol on conditionally immortalized human fetal osteoblasts (hFOB) in culture. Ethanol treatment had no significant effects on osteoblast number after 1 day or 7 days. Ethanol treatment did not reduce type I collagen protein levels at either time point at any dose but slightly reduced alkaline phosphatase activity after 7 days. The messenger RNA (mRNA) levels for alkaline phosphatase, type I collagen, and osteonectin were unaltered by 24 h of ethanol treatment but a high dose (200 mM) reduced mRNA levels for the two bone matrix proteins after 7 days. Ethanol treatment led to dose-dependent increases in transforming growth factor beta1 (TGF-beta1) mRNA levels and decreases in TGF-beta2 mRNA levels. The concentration of ethanol in the medium decreased with time because of evaporation but there was little degradation caused by metabolism. These results, which show that cultured osteoblasts are less sensitive than osteoblasts in vivo, suggest that the pronounced inhibitory effects of ethanol on bone formation are not caused by direct cell toxicity.
Maran
A
A
Department of Orthopedics, Mayo Clinic, Rochester, Minnesota 55905, USA.
Zhang
M
M
Spelsberg
T C
TC
Turner
R T
RT
D000469:Alkaline Phosphatase / Q000235:genetics; D002460:Cell Line; D003094:Collagen / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005333:Fetus / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015676:Osteonectin / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015676:Osteonectin; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000431:Ethanol; D003094:Collagen; D000469:Alkaline Phosphatase