Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: A possible role of oxidative stress
Histomorphometric analysis of diabetic osteopenia in streptozotocin-induced diabetic mice: A possible role of oxidative stress
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DOI：
10.1016/j.bone.2006.12.057
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发表时间：
2007-05-01
期刊：
影响因子：
4.1
通讯作者：
Fukagawa, Masafumi
中科院分区：
文献类型：
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作者：
Hamada, Yasuhiro;Kitazawa, Sohei;Fukagawa, Masafumi
糖尿病骨量减少会导致骨折的增加和骨折愈合的延迟，影响生活质量。然而，导致这种疾病的机制还没有明确确定。氧化应激可能是发病机制的一个潜在候选因素，因为它在糖尿病条件下会增加，并已知会导致多种细胞类型的细胞功能障碍。虽然体外研究表明氧化应激抑制成骨细胞分化，诱导成骨细胞损伤和凋亡，但糖尿病骨量减少与氧化应激之间的关系尚不清楚。为了探索这些问题，有必要对代表糖尿病患者骨量减少的小鼠模型进行分析。然而，关于这种模式的报道很少。因此，我们重点研究了链脲佐菌素(STZ)诱导的糖尿病小鼠，这是最常见的I型糖尿病动物模型之一。8周龄雄性C57BL/6小鼠随机分为3组：1)对照组，2)糖尿病组，3)胰岛素治疗糖尿病组。STZ治疗12周后，检测STZ糖尿病小鼠(STZ-小鼠)股骨的物理性质、静态和动态骨形态计量学参数，并评价小鼠全身和骨骼的氧化应激。在实验期结束时，所有三组的肾功能都是相似的。此外，三组间血清甲状旁腺素、钙、磷均无显著差异。相反，放射学分析显示骨小梁体积显著减少，组织形态计量学分析证实，STZ-小鼠的骨形成参数(OV/BV、OS/BS和BFR/BS)和骨吸收参数(ES/BS和Oc.S/BS)也显著降低。此外，STZ-小鼠的尿中8-羟基脱氧鸟苷排泄量增加，这是DNA氧化损伤的标志。进一步的免疫组织学研究显示，在糖尿病小鼠的骨组织中，包括成骨细胞在内的一种氧化应激标志物的免疫染色增强。在这里，我们证明了STZ-小鼠表现出与氧化应激增加相关的低周转性骨量减少。(C)2006 Elsevier Inc.保留所有权利。
Diabetic osteopenia causes an increase in bone fracture and a delay in healing of fractures, and affects the quality of life. However, the mechanisms responsible for the disease have not been clearly identified. Oxidative stress may be a potential candidate for the pathogenesis, since it is increased under diabetic conditions and is known to induce cellular dysfunction in a wide variety of cell types. Although in vitro studies have shown that oxidative stress inhibits osteoblastic differentiation and induces osteoblast insults and apoptosis, the relationship between diabetic osteopenia and oxidative stress remains unclear. To explore these issues, analysis of a mouse model that represents the diabetic osteopenia as seen in patients with diabetes is necessary. However, there are few reports of such a model. Therefore, we focused on the streptozotocin (STZ)-induced diabetic mouse, one of the most common animal models of type I diabetes. Eight-week-old male C57BL/6 mice were randomly assigned to the following three groups: 1) control group, 2) diabetic group, and 3) insulin-treated diabetic group. After 12 weeks of STZ treatment, the physical properties of the femora, and the static and dynamic parameters of bone histomorphometry of the tibiae from STZ-induced diabetic mice (STZ-mice) were assessed, and oxidative stress in the whole body and bone of the mice was evaluated. Renal function was comparable in all three groups at the end of the experimental period. In addition, no significant difference in serum PTH, Ca, and P was found among the three groups. In contrast, radiological analysis demonstrated a significant decrease in trabecular bone volume, and histomorphometric analyses confirmed that parameters for both bone formation (OV/BV, OS/BS, and BFR/BS) and bone resorption (ES/BS and Oc.S/BS) were also significantly lower in STZ-mice. In addition, urinary excretion of 8-hydroxydeoxyguano sine, a marker of oxidative DNA damage, was elevated in STZ-mice. Further immunohistological studies showed intensified immunostaining of an oxidative stress marker in bone tissue including the osteoblasts of diabetic mice. Here, we demonstrated that STZ-mice exhibit low-turnover osteopenia associated with increased oxidative stress. (c) 2006 Elsevier Inc. All rights reserved.