Effects of ethanol on gene expression in rat bone: transient dose-dependent changes in mRNA levels for matrix proteins, skeletal growth factors, and cytokines are followed by reductions in bone formation.
Effects of ethanol on gene expression in rat bone: transient dose-dependent changes in mRNA levels for matrix proteins, skeletal growth factors, and cytokines are followed by reductions in bone formation.
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乙醇对大鼠骨骼中基因表达的影响:基质蛋白、骨骼生长因子和细胞因子的 mRNA 水平发生短暂的剂量依赖性变化,随后骨形成减少。
DOI:
10.1111/j.1530-0277.1998.tb03953.x
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发表时间:
1998
期刊:
影响因子:
--
通讯作者:
Sibonga,JD
中科院分区:
文献类型:
--
作者:
Turner,RT;Wronski,TJ;Zhang,M;Kidder,LS;Bloomfield,SA;Sibonga,JD
Several studies were performed in female rats to determine dose and time course changes in mRNA levels for matrix proteins in bone after a single administration of ethanol. As expected, dose‐dependent transient increases in blood ethanol were measured. Additionally, there was mild hypocalcemia with no change in immunoreactive parathyroid hormone. Coordinated dose‐dependent increases in mRNA for type 1 collagen, osteonectin, and osteocalcin were noted in the proximal tibial metaphysis 6 hr after ethanol was given, with the peak values occurring at a dose of 1.2 g/kg (0.4 ml). Similar increases in mRNA levels for matrix proteins were noted in lumbar vertebrae after ethanol treatment. The changes were specific for bone; ethanol had no effect on mRNA levels for matrix proteins in the uterus or liver, although the mRNA concentrations tended to be reduced in uterus. Message levels for several cytokines implicated in the regulation of bone turnover were also assayed; mRNA levels for transforming growth factor‐β1, transforming growth factor‐β2, interferon‐γ, and interleukin‐6 were unchanged at doses ranging from 0.14 to 1.7 g/kg. At the highest dose of ethanol, the mRNA level for tumor necrosis factor‐α was elevated while the level for insulin‐like growth factor‐1 was reduced. The time course effects of ethanol (0.4 ml dose) were determined in a separate experiment. Ethanol resulted in a transient increase in mRNA levels for the three bone matrix proteins assayed. However, matrix protein synthesis, as determined by incorporation of3H‐proline into the proximal tibial metaphysis, was not changed after 6 hr. The changes in mRNA levels for the matrix proteins were preceded by brief, transient decreases in mRNA levels for interleukin‐1 β, interferon‐γ, and migration inhibitory factor, and followed by a more prolonged decrease in the mRNA level for insulin‐like growth factor‐1. A subsequent study was performed to determine the effects of repetitive daily treatment with ethanol on rat bone. After 7 days, there were highly significant decreases in the mRNA level for type 1 collagen, as well as decreased bone formation. These results suggest that ethanol may alter bone metabolism by disturbing signal transduction pathways that regulate the expression of genes for bone matrix proteins, skeletal growth factors, and cytokines.
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影响因子:
4.8
作者:
Westerlind,KC;Wakley,GK;Evans,GL;Turner,RT
通讯作者:
Turner,RT
DOI:
10.1210/endo.138.4.5040
发表时间:
1997
期刊:
Endocrinology.
影响因子:
--
作者:
Cavolina,JM;Evans,GL;Harris,SA;Zhang,M;Westerlind,KC;Turner,RT
通讯作者:
Turner,RT
DOI:
10.1111/j.1530-0277.1988.tb00260.x
发表时间:
1988
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
作者:
Peng,TC;Kusy,RP;Hirsch,PF;Hagaman,JR
通讯作者:
Hagaman,JR
DOI:
10.1016/s0169-6009(08)80134-1
发表时间:
1994
期刊:
Bone and Mineral
影响因子:
--
作者:
K. Laitinen;R. Tähtelä;K. Luomanmäki;M. Välimäki
通讯作者:
M. Välimäki
DOI:
10.1111/j.1530-0277.1988.tb00152.x
发表时间:
1988
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
作者:
Turner,RT;Aloia,RC;Segel,LD;Hannon,KS;Bell,NH
通讯作者:
Bell,NH