Age-related bone loss in the LOU/c rat model of healthy ageing

Age-related bone loss in the LOU/c rat model of healthy ageing
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DOI:
10.1016/j.exger.2008.10.004
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发表时间:
2009-03-01
影响因子:
3.9
通讯作者:
Gaudreau, Pierrette
Gaudreau, Pierrette
中科院分区:
医学2区
文献类型:
--
作者:
Duque, Gustavo;Rivas, Daniel;Gaudreau, Pierrette

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近交系白化大鼠(LOU)被认为是健康老龄化的模型,因为它们在没有肥胖的情况下寿命更长,而且常见的与年龄相关的疾病的发病率很低。在这项研究中,我们利用定量的显微计算机断层扫描(MCT)成像、组织学和循环骨生物标志物的生化分析,研究了4、20和27个月龄的Lou雄性和雌性Lou大鼠的骨表型。由MCT评估的股骨远端的骨质量和形态计量学,在4月龄的雄性和雌性大鼠中是相似的,并且随着时间的推移而恶化。未脱钙骨的组织化学染色显示,20个月龄时皮质和松质骨明显减少。矿化组织的减少伴随着成骨细胞和破骨细胞数量的减少以及骨髓肥胖症的显着增加。骨转换的生化标志物,C-端肽和骨钙素,与年龄相关的骨丢失相关,而促钙激素PTH和维生素D随着时间的推移保持不变。综上所述,老年Lou大鼠表现出低周转率的骨丢失和骨髓脂肪渗透,这是老年性骨质疏松症的特征,因此是研究导致这种疾病的分子机制的新模型。(C)2008 Elsevier Inc.保留所有权利。
Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder. (C) 2008 Elsevier Inc. All rights reserved.