The analysis of bone related diseases in cranio and oro-maxillofacial region by using A170 gene knockout mouse

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The purpose of this study is to elucidate the role of A170 gene, which is causative gene of Paget's disease of bone, in the bone related diseases in cranio-oro-maxillofacial region by using A170 gene knockout mouse.At first, we repeated backcross of knockout mice because the value of bone morphometry was not constant. While backcross was undergoing, we analyzed the phenotype of Nrf2 knockout mouse, because Nrf2 was transcription factor of oxidative stress inducible proteins and Nrf2deficient mouse lacks A170 induction. Since Peroxiredoxin I was regulated by Nrf2, we measured the elimination capacity of reactive oxygen species in Peroxiredoxin I deficient mouse to prepare estimation of oxidative stress in A170 knockout mouse.After backcross was repeated, we performed bone morphometry. The parameters of bone morphometry : osteoid surface, osteoid thickness, eoroded surface, osteoclast surface, trabecular number, mineral apposition rate, and bone formation rate were significantly different between knockout mouse and wild type mouse. The osteoblast from calvaria of mouse embryo was cultured, and alkaline phosphatase activity and Arizarin Red-S staining density were measured. There was tendency that the osteoblastic activity was lower in the knockout mice. The other phenotypes of A170 gene knockout mouse were hyperphagia, obesity, and insulin resistance. Insulin resistance was proved by-glucose and insulin loaded test. Glucose uptake was proved to be reduced by using isotope labeled 2-deoxyglucose. From those results osteoblastic function was damaged in A170 knockout mouse and insulin signal may be associated with this phenomenon.