Friday, January 23, 2009

Aldehyde Dehydrogenase 2

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

"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. Alcohol consumption results in decreased trabecular bone volume in aldh2 knockout (aldh2(-/-)) mice compared with the volume in wild-type (aldh2(+/+)) mice.
We examined aldh2(-/-) and aldh2(+/+) mice at the ages of 4, 8 and 12week 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. mRNA expression in aldh2(-/-) and aldh2(+/+) mice after tail suspension or climbing exercise for 7days from 8weeks was analyzed to clarify the response to mechanical loading.
At 12weeks, 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 8weeks, 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 col1a1 mRNA in aldh2(-/-) mice, along with an increase in the expression of wnt5a mRNA and the lrp5/sost mRNA ratio. The mRNA expressions of bmp2, osterix, runx2 and pthr in aldh2(-/-) mice were significantly decreased after climbing exercise compared to those in the control, although the mRNA expressions of bmp2, osterix, runx2 were not significantly decreased and pth mRNA expression was increased in aldh(+/+) mice after climbing exercise."

"aldh2−/− mice that consume alcohol show decreased trabecular bone volume because of alcohol-induced reduction of bone formation associated with elevated p21 expression in bone marrow cells"

There was a very minor non-statistically sigificant decrease in femoral bone length in Aldh2-/- mice at 8 and 12 weeks.

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