Analyses of Nedd4 deficient mice showing significant bone loss

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462304
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Miyazaki
• Principal Investigator: Sekimoto Tomohisa 宮崎大学, 医学部, 講師 (60305000)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: Nedd4遺伝子 / 骨代謝機能 / 骨芽細胞 / 可変型遺伝子トラップ法 / ロコモティブシンドローム / モデルマウス

Outline of Final Research Achievements

We analyzed the bone phenotype of Nedd4 gene trap line produced by the exchageable gene trap method. Nedd4 has not been previously reported enough on bone metabolism in vivo. We underwent micro-CT imaging, bone morphometry analysis (BMA), bone strength analysis (BSA), various staining of bone tissue specimens, microarray analysis, osteoblast culture and realtime PCR. Nedd4 trap mouse analysis confirmed loss of trabeculae on micro-CT images, significant decrease in bone volume for almost all parameters in BMD analysis, cortical bone analysis, and trabecular bone analysis in BMA, and also indicated significant bone fragility in BSA. Real-time PCR showed that expression of the osteoblast differentiation markers Col1a1 and ALP significantly decreased compared with WT. In microarray analysis, Col1a1 and Runx2 decreased compared with WT. In osteoblast culure, Col1a1, Runx2, OCN and ALP also decreased. From these results, it was suggested that Nedd4 is involved in the function of osteoblasts.

Free Research Field

整形外科学