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A novel rat model for the study of deficits in bone formation in type-2 diabetes.

机译:研究2型糖尿病骨骼形成缺陷的新型大鼠模型。

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BACKGROUND: There is evidence to suggest that impairment in bone formation and/or turnover is associated with the metabolic abnormalities characteristic of type-2 diabetes mellitus. However, bone regeneration/repair in type-2 diabetes has not been modeled. Using Zucker Diabetic Fatty (ZDF) rats (a model of type-2 diabetes) for tibial distraction osteogenesis (DO), we hypothesized that bone formation within the distraction gap would be impaired. ANIMALS AND METHODS: Rats were examined for body weight, glycosuria, and glycosemia to confirm the diabetic condition during the study. The rats received placement of the external fixators and osteotomies on the left tibia. Distraction was initiated the following day at 0.2 mm twice a day and continued for 14 days. The lengthened tibiae were harvested and distraction gaps were examined radiographically and histologically. RESULTS: We found significant reduction in new bone formation in the distraction gaps of the ZDF rats, both radiographically and histologically, compared to lean rats. We found a decrease in a marker of cellular proliferation in the distraction gaps and increased adipose volume in adjacent bone marrow of the ZDF rats. INTERPRETATION: Our findings suggest that this model might be used to study the contributions of leptin resistance, insulin resistance and/or hyperglycemia to impaired osteoblastogenesis in vivo.
机译:背景:有证据表明,骨形成和/或更新障碍与2型糖尿病的代谢异常有关。但是,尚未对2型糖尿病的骨再生/修复进行建模。使用Zucker糖尿病脂肪(ZDF)大鼠(2型糖尿病模型)进行胫骨牵张成骨(DO),我们假设牵张间隙内的骨形成会受到损害。动物和方法:检查大鼠的体重,糖尿和糖血症,以确认研究期间的糖尿病状况。大鼠接受左胫骨外固定器和截骨术的放置。第二天以每天两次0.2 mm的距离开始分散注意力,并持续14天。收集加长的胫骨,并通过影像学和组织学检查撑开间隙。结果:与瘦大鼠相比,无论从影像学还是组织学上来说,ZDF大鼠的牵引间隙中新骨形成的显着减少。我们发现ZDF大鼠分散间隙中细胞增殖的标志物减少,而相邻骨髓的脂肪量增加。解释:我们的发现表明,该模型可用于研究瘦素抵抗,胰岛素抵抗和/或高血糖对体内成骨细胞生成受损的影响。

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