Oxidative stress in bone regulates skeletal homeostasis in mice

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462283
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Chiba University
• Principal Investigator: Shimizu Takahiko 千葉大学, 大学院医学研究院, 特任准教授 (40301791)
• Co-Investigator(Renkei-kenkyūsha): NOJIRI Hidetoshi 順天堂大学, 医学部, 准教授 (10317456)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 骨 / 酸化ストレス / 老化 / SOD / 骨格筋

Outline of Final Research Achievements

Superoxide dismutase 2 (Sod2) is a mitochondrial antioxidant enzyme that plays a pivotal role in the maintenance of mitochondrial function to regulate redox balance. However, the physiological function of Sod2 in bone metabolism has not been fully elucidated. In order to address this question, mice lacking Sod2 in osteocytes were generated by crossbreeding mice harboring a Sod2 conditional allele with Dmp1-Cre transgenic mice (Dmp1-Sod2-/-). The Sod2 ablation in osteocytes significantly caused bone loss and fragility in an age-dependent manner. In addition, histomorphometric analyses also revealed that Sod2 loss markedly disorganized bone canaliculi in the cortical bones, indicating osteocyte dysfunction. Interestingly, we found specific up-regulation of Sost and Rankl genes in bone. These findings demonstrated that mitochondrial SOD in osteocytes regulates osteocyte fate and RANKL- and Sclerostin-mediated bone metabolism in mice.

Free Research Field

運動器老化