Liu Zhendong, Aronson James, Wahl Elizabeth C, Liu Lichu, Perrien Daniel S, Kern Phillip A, Fowlkes John L, Thrailkill Kathryn M, Bunn Robert C, Cockrell Gael E, Skinner Robert A, Lumpkin Charles K
Laboratory for Limb Regeneration Research, Arkansas Children's Hospital Research Institute, Little Rock, AR, USA.
Acta Orthop. 2007 Feb;78(1):46-55. doi: 10.1080/17453670610013411.
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.
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.
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.
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.
有证据表明，骨形成和/或骨转换受损与2型糖尿病的代谢异常特征相关。然而，尚未建立2型糖尿病中的骨再生/修复模型。我们使用Zucker糖尿病脂肪大鼠（ZDF大鼠，一种2型糖尿病模型）进行胫骨牵张成骨（DO），推测牵张间隙内的骨形成会受损。
在研究期间检查大鼠的体重、糖尿和血糖，以确认糖尿病状况。大鼠接受左侧胫骨外固定器植入和截骨术。次日开始牵张，每天两次，每次0.2毫米，持续14天。收集延长后的胫骨，对牵张间隙进行影像学和组织学检查。
与瘦大鼠相比，我们发现ZDF大鼠牵张间隙内的新骨形成在影像学和组织学上均显著减少。我们发现ZDF大鼠牵张间隙内细胞增殖标志物减少，相邻骨髓中的脂肪体积增加。
我们的研究结果表明，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。
