Disruption of aldehyde dehydrogenase 2 gene results in altered cortical bone structure and increased cortical bone mineral density in the femoral diaphysis of mice

Abstract Introduction Aldehyde dehydrogenase 2 (ALDH2) degrades acetaldehyde produced by the metabolism of alcohol. The inactive ALDH2 phenotype is prevalent in East Asians, and an association between this ALDH2 polymorphism and osteoporosis has been reported. In our previous study, we found that alcohol consumption results in decreased trabecular bone volume in aldh2 knockout ( aldh2−/− ) mice compared with the volume in wild-type ( aldh2+/+ ) mice. However, the effect of aldh2 gene on the skeletal phenotype in the absence of alcohol consumption remains unknown. The aim of this study was to clarify the effect of aldh2 disruption on femoral bone structure and dynamics in aldh2 -disrupted mice in the absence of alcohol consumption. Materials and methods We examined aldh2−/− and aldh2+/+ mice at the ages of 4, 8 and 12 weeks. The femoral bone length and bone mineral density (BMD) were measured using peripheral quantitative computed tomography. The mechanical strength was assessed by the three-point bending test at 12 weeks, and cortical bone histomorphometry at the femur diaphysis was performed at all three time points. Osteogenic activities in aldh2−/− and aldh2+/+ mice were assessed by osteoblast culture from calvariae of the neonatal mice. Bilateral femoral and tibial bones containing no bone marrow cells of 8-week-old mice were used for analysis of mRNA expression. In addition, mRNA expression in aldh2−/− and aldh2+/+ mice after tail suspension or climbing exercise for 7 days from 8 weeks was analyzed to clarify the response to mechanical loading. Results At 12 weeks, there were no significant differences in femoral bone length, trabecular BMD in the distal metaphyses of the femurs, or mechanical strength between aldh2−/− and aldh2+/+ mice, whereas cortical BMD and cortical thickness were significantly increased and cross-sectional area and bone marrow area were significantly decreased in the femoral diaphysis of aldh2−/− mice relative to the corresponding values in aldh2+/+ mice. At 8 weeks, bone formation rate and mineral apposition rate on the periosteal and endocortical surfaces were significantly increased in aldh2−/− mice relative to the rates in aldh+/+ mice. Calvarial osteoblast culture study revealed that the percentage of alkaline phosphatase stained cells was significantly higher in aldh2−/− mice compared to that in aldh+/+ mice. Quantitative real-time RT-PCR revealed a significant increase in the expressions of bmp2 , osterix, runx2, and col1