Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro.

Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro.
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DOI:
10.1186/s13018-018-0800-7
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发表时间:
2018-04-27
影响因子:
2.6
通讯作者:
Callaci JJ
Callaci JJ
中科院分区:
医学3区
文献类型:
--
作者:
Natoli RM;Yu H;Meislin MC;Abbasnia P;Roper P;Vuchkovska A;Xiao X;Stock SR;Callaci JJ

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饮酒是影响骨折愈合的一个危险因素,尽管发生这种情况的机制(S)还不清楚。我们的实验室以前已经表明,啮齿动物间歇性酒精暴露对骨折骨痂的发育、骨痂生物力学和调节干细胞分化的细胞信号产生负面影响。在这里,我们研究了酒精是否改变了小鼠骨折愈合早期骨痂中趋化因子的表达和/或信号活性。采用酒精损伤的小鼠胫骨骨折愈合模型。研究了早期骨折骨痂中酒精对组织成分、参与MSC迁移到骨折部位的趋化因子的表达以及生物力学的影响。在体外系统中检测酒精对MSC迁移和细胞黏附受体的影响。暴露在酒精中的小鼠表现出外部骨痂形成的证据减少,骨痂相关骨桥蛋白(OPN)表达水平降低,生物力学硬度降低。酒精暴露可降低重组骨桥蛋白介导的骨髓间充质干细胞迁移和整合素β1受体的表达。酒精暴露对骨折骨痂相关骨桥蛋白表达、重组骨桥蛋白介导的体外骨髓间充质干细胞迁移以及骨髓间充质干细胞整合素β-1受体表达的影响尚未见报道。了解酒精暴露对骨折修复早期阶段的影响可能有助于及时开始治疗,以减少延迟愈合和/或骨折不愈合的长期并发症。
Alcohol consumption is a risk factor for impaired fracture healing, though the mechanism(s) by which this occurs are not well understood. Our laboratory has previously shown that episodic alcohol exposure of rodents negatively affects fracture callus development, callus biomechanics, and cellular signaling which regulates stem cell differentiation. Here, we examine whether alcohol alters chemokine expression and/or signaling activity in the mouse fracture callus during early fracture healing. A mouse model for alcohol-impaired tibia fracture healing was utilized. Early fracture callus was examined for alcohol-effects on tissue composition, expression of chemokines involved in MSC migration to the fracture site, and biomechanics. The effects of alcohol on MSC migration and cell adhesion receptors were examined in an in vitro system. Mice exposed to alcohol showed decreased evidence of external callus formation, decreased callus-related osteopontin (OPN) expression levels, and decreased biomechanical stiffness. Alcohol exposure decreased rOPN-mediated MSC migration and integrin β1 receptor expression in vitro. The effects of alcohol exposure demonstrated here on fracture callus-associated OPN expression, rOPN-mediated MSC migration in vitro, and MSC integrin β1 receptor expression in vitro have not been previously reported. Understanding the effects of alcohol exposure on the early stages of fracture repair may allow timely initiation of treatment to mitigate the long-term complications of delayed healing and/or fracture non-union.
DOI: 10.1093/alcalc/agq030
发表时间: 2010-07-01
影响因子: 2.8
作者:
Callaci, John J.;Himes, Ryan;Roper, Phillip
通讯作者: Roper, Phillip
DOI: 10.1371/journal.pmed.0040249
发表时间: 2007-07-31
期刊: PLoS medicine
影响因子: 15.8
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DOI: 10.1097/01.alc.0000118315.58404.c1
发表时间: 2004-03-01
影响因子: 3.2
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Gong, ZD;Wezeman, FH
通讯作者: Wezeman, FH
DOI: 10.1302/0301-620x.93b6.26432
发表时间: 2011-06-01
影响因子: --
作者:
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通讯作者: Keating, J. F.
DOI: 10.1111/j.1530-0277.2002.tb02568.x
发表时间: 2002-04-01
影响因子: 3.2
作者:
Elmali, N;Ertem, K;Bora, A
通讯作者: Bora, A