Elucidation of impaired bone homeostasis mechanism by mutation of Acetaldehyde Dehydrogenase2 gene(ALDH2)

大约一半的日本人有一个突变的ALDH 2基因，导致对酒精敏感。在统计分析报告中，ALDH 2基因的突变加速骨质疏松。然而，突变基因ALDH 2如何影响骨形成的机制仍然未知。本研究利用ALDH 2-DAL小鼠研究ALDH 2基因突变与骨稳态的关系。ALDH 2-DAL小鼠表现出骨质疏松症，并显示骨密度显著降低。在形态计量学分析中，与野生型小鼠相比，ALDH 2-DAL骨小梁和皮质骨厚度更薄，骨形成和矿化率也降低。细胞染色显示ALDH 2基因突变小鼠成骨细胞数量较野生型明显减少。与野生型成骨细胞相比，具有突变ALDH 2-DAL基因的小鼠的成骨细胞分化的标记基因的表达降低。

About half of the Japanese have a mutant ALDH2 gene, resulting to sensitivity to alcohol. In statistical analysis report, a mutation of the ALDH2 gene accelerates osteoporosis. However, the mechanism on how the mutated gene ALDH2 affects bone formation is still unknown. In this study, I try to work out the relation between the mutation of the ALDH2 gene and bone homeostasis by utilizing inactive ALDH2(ALDH2-DAL) mice. ALDH2-DAL mice exhibited osteoporosis and showed significantly reduced bone density. In morphometrical analysis, ALDH2-DAL trabecular and cortical bone thickness were thinner, and bone formation and mineralized rates were also decreased compared to that of wild type mice. Osteoblast in mice with mutated ALDH2 gene remarkably decreased compared to wild type osteoblasts by cell staining. The expression of marker genes on osteoblast differentiation of mice with mutated ALDH2-DAL gene was decreased compared to wild type osteoblasts.