A novel mouse model for the study of the inhibitory effects of chronic ethanol exposure on direct bone formation
A novel mouse model for the study of the inhibitory effects of chronic ethanol exposure on direct bone formation
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DOI：
10.1016/j.alcohol.2006.08.004
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发表时间：
2006-07-01
期刊：
影响因子：
2.3
通讯作者：
Lumpkin, Charles K., Jr.
中科院分区：
文献类型：
--
作者：
Wahl, Elizabeth C.;Liu, Lichu;Lumpkin, Charles K., Jr.
据报道，过量饮酒会以多种方式干扰人体骨稳态和修复。先前的研究表明，大鼠通过胃内饮食递送系统的慢性乙醇暴露抑制牵张成骨（DO，肢体延长）过程中的直接骨形成。由于DO小鼠模型的开发，现在有可能将大鼠乙醇研究扩展到小鼠。本研究采用了一种新的液体乙醇饮食递送和小鼠DO模型的组合，以检验以下假设：与成对喂养对照相比，慢性乙醇暴露将导致DO期间直接骨形成的缺陷。使28只12月龄C57 BL/6雄性小鼠适应Lieber-DeCarli液体对照饮食#710027（Dyets Inc.）在一周内。将小鼠分成两个饮食组（n = 14/组）：成对喂食对照和乙醇（饮食#710260）。在饮食82天后，所有小鼠都接受了外固定器的放置和左胫骨截骨术。在6天的潜伏期之后，以0.075 mm的速率每天两次（b.i.d.）14天。两组的体重变化相当。影像学结果支持慢性乙醇暴露会抑制直接骨形成并产生骨骼毒性的假设。（P = .011）和组织学（P = .002）DO间隙中新骨形成%的分析，通过外周定量计算机断层扫描分析对侧胫骨近端的总体积骨密度通过对侧胫骨的三点弯曲（P < .001），通过钉部位骨形成测量（P <.001），以及通过乙醇相关的脂肪细胞面积（邻近差距）百分比增加（P <.002），对侧股骨颈（P =.012）进行了比较。我们的结论是，该模型可用于研究慢性乙醇暴露抑制骨形成的机制并测试临床前干预措施。(c)2006年爱思唯尔公司All rights reserved.
Excessive alcohol consumption has been reported to interfere with human bone homeostasis and repair in multiple ways. Previous studies have demonstrated that chronic ethanol exposure in the rat via an intragastric dietary delivery system inhibits direct bone formation during distraction osteogenesis (DO, limb lengthening). The opportunity to extend the rat ethanol studies to mice is now possible due to the development of mouse models of DO. This study employed a novel combination of liquid ethanol diet delivery and a murine DO model to test the hypothesis that chronic ethanol exposure would result in deficits in direct bone formation during DO in contrast to the pair-fed controls. Twenty-eight 12-month-old C57BL/6 male mice were acclimated to the Lieber-DeCarli liquid control diet #710027 (Dyets Inc.) over a 1-week period. The mice were separated into two diet groups (n = 14/group): pair-fed control and ethanol (diet #710260). After being on diet for 82 days, all mice underwent placement of an external fixator and osteotomy on the left tibia. Following a 6-day latency period, distraction began at a rate of 0.075 mm twice a day (b.i.d.) for 14 days. The weight changes were equivalent for both groups. The hypothesis that chronic ethanol exposure would inhibit direct bone formation and produce skeletal toxicity was supported by radiographic (P = .011) and histologic (P = .002) analyses of the % new bone formation in the DO gaps, by peripheral quantitative computed tomography analysis of the total volumetric bone mineral density of the contralateral proximal tibias (P < .001) and contralateral femoral necks (P = .012), by three-point bending on the contralateral tibias (P < .001 energy to break), by pin site bone formation measures (P < .001), and by ethanol-associated increased adipocyte area (adjacent to the gap) percentages (P < .002). We conclude that this model can be used to study the mechanisms underlying inhibition of bone formation by chronic ethanol exposure and to test preclinical interventions. (c) 2006 Elsevier Inc. All rights reserved.