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The Effect of Ethanol Consumption on Composition and Morphology of Femur Cortical Bone in Wild-Type and ALDH2*2-Homozygous Mice
Calcified Tissue International ( IF 3.3 ) Pub Date : 2020-10-17 , DOI: 10.1007/s00223-020-00769-1
Andrey V Malkovskiy 1, 2 , Lauren D Van Wassenhove 2 , Yury Goltsev 3 , Kwame Osei-Sarfo 4 , Che-Hong Chen 2 , Bradley Efron 5 , Lorraine J Gudas 4 , Daria Mochly-Rosen 2 , Jayakumar Rajadas 1
Affiliation  

ALDH2 inactivating mutation (ALDH2*2) is the most abundant mutation leading to bone morphological aberration. Osteoporosis has long been associated with changes in bone biomaterial in elderly populations. Such changes can be exacerbated with elevated ethanol consumption and in subjects with impaired ethanol metabolism, such as carriers of aldehyde dehydrogenase 2 (ALDH2)-deficient gene, ALDH2*2. So far, little is known about bone compositional changes besides a decrease in mineralization. Raman spectroscopic imaging has been utilized to study the changes in overall composition of C57BL/6 female femur bone sections, as well as in compound spatial distribution. Raman maps of bone sections were analyzed using multilinear regression with these four isolated components, resulting in maps of their relative distribution. A 15-week treatment of both wild-type (WT) and ALDH2*2/*2 mice with 20% ethanol in the drinking water resulted in a significantly lower mineral content (p < 0.05) in the bones. There was no significant change in mineral and collagen content due to the mutation alone (p > 0.4). Highly localized islets of elongated adipose tissue were observed on most maps. Elevated fat content was found in ALDH2*2 knock-in mice consuming ethanol (p < 0.0001) and this effect appeared cumulative. This work conclusively demonstrates that that osteocytes in femurs of older female mice accumulate fat, as has been previously theorized, and that fat accumulation is likely modulated by levels of acetaldehyde, the ethanol metabolite.



中文翻译:


乙醇消耗对野生型和 ALDH2*2 纯合子小鼠股骨皮质骨组成和形态的影响



ALDH2失活突变(ALDH2*2)是导致骨形态畸变的最丰富的突变。骨质疏松症长期以来一直与老年人群骨生物材料的变化有关。这种变化会随着乙醇消耗量的增加以及乙醇代谢受损的受试者(例如乙醛脱氢酶 2 (ALDH2) 缺陷基因 ALDH2*2 的携带者)而加剧。到目前为止,除了矿化减少之外,人们对骨成分的变化知之甚少。拉曼光谱成像已用于研究 C57BL/6 女性股骨切片整体组成的变化以及复合空间分布。使用多线性回归对这四个独立组件进行骨切片的拉曼图分析,从而得到它们的相对分布图。用饮用水中的 20% 乙醇对野生型 (WT) 和 ALDH2*2/*2 小鼠进行为期 15 周的治疗,导致骨​​骼中矿物质含量显着降低 ( p < 0.05)。仅由于突变,矿物质和胶原蛋白含量没有显着变化 ( p > 0.4)。在大多数地图上都观察到高度局部化的细长脂肪组织胰岛。在消耗乙醇的 ALDH2*2 敲入小鼠中发现脂肪含量升高 ( p < 0.0001),并且这种效应似乎是累积的。这项工作最终证明,正如之前的理论,老年雌性小鼠股骨中的骨细胞会积累脂肪,并且脂肪积累可能受到乙醛(乙醇代谢物)水平的调节。

更新日期:2020-10-17
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