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酒精暴露会降低骨折愈合过程中骨桥蛋白的表达以及体外骨桥蛋白介导的间充质干细胞迁移。

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

作者信息

Natoli Roman M, Yu Henry, Meislin Megan Conti-Mica, Abbasnia Pegah, Roper Philip, Vuchkovska Aleksandra, Xiao Xianghui, Stock Stuart R, Callaci John J

机构信息

Department of Orthopaedic Surgery and Rehabilitation, Stritch School of Medicine, Loyola University Chicago, 2160 South First Ave, Maywood, IL, 60153, USA.

Present Address: Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

出版信息

J Orthop Surg Res. 2018 Apr 27;13(1):101. doi: 10.1186/s13018-018-0800-7.

DOI:10.1186/s13018-018-0800-7
PMID:29699560
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5921778/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

饮酒是骨折愈合受损的一个风险因素，尽管其发生机制尚未完全明确。我们实验室先前已表明，啮齿动物间歇性接触酒精会对骨折痂发育、痂生物力学以及调节干细胞分化的细胞信号传导产生负面影响。在此，我们研究酒精是否会在骨折愈合早期改变小鼠骨折痂中的趋化因子表达和/或信号传导活性。

方法

采用酒精影响小鼠胫骨骨折愈合的模型。检查早期骨折痂，以了解酒精对组织组成、参与间充质干细胞迁移至骨折部位的趋化因子表达以及生物力学的影响。在体外系统中研究酒精对间充质干细胞迁移和细胞黏附受体的影响。

结果

接触酒精的小鼠显示出外部骨痂形成的证据减少、与骨痂相关的骨桥蛋白（OPN）表达水平降低以及生物力学硬度降低。酒精暴露在体外降低了rOPN介导的间充质干细胞迁移和整合素β1受体表达。

结论

本文所展示的酒精暴露对骨折痂相关OPN表达、体外rOPN介导的间充质干细胞迁移以及体外间充质干细胞整合素β1受体表达的影响此前尚未见报道。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，以减轻延迟愈合和/或骨折不愈合的长期并发症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/d382b25c9337/13018_2018_800_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/6cee8e051841/13018_2018_800_Fig4_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/91a24bf6449e/13018_2018_800_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/d382b25c9337/13018_2018_800_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/b5df2888462f/13018_2018_800_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/3b37101c0137/13018_2018_800_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/72a296403be3/13018_2018_800_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/6cee8e051841/13018_2018_800_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/346b91840910/13018_2018_800_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/814d1cfeda3e/13018_2018_800_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/91a24bf6449e/13018_2018_800_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db3/5921778/d382b25c9337/13018_2018_800_Fig8_HTML.jpg

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