The role of oxidative stress in the maintenance of bone metabolism

2014 Fiscal Year Final Research Report

• Project/Area Number: 24791568
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Juntendo University
• Principal Investigator: SAITA Yoshitomo 順天堂大学, 医学部, 助教 (00534885)
• Co-Investigator(Kenkyū-buntansha): NOJIRI Hidetoshi 順天堂大学, 整形外科, 助教 (10317456)
• Co-Investigator(Renkei-kenkyūsha): SHIMIZU Takahiko 千葉大学, 大学院医学研究院先進加齢医学講座, 准教授 (40301791)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 酸化ストレス / 骨粗鬆症 / 骨細胞

Outline of Final Research Achievements

Osteocytes play a crucial role in maintaining the quality of and healing damage to bone tissue. However, the pathological effects of mitochondrial redox imbalances on osteocytes and bone metabolism have not been fully elucidated. We generated mice lacking mitochondrial superoxide dismutase 2 (Sod2) in osteocytes. Sod2 depletion in the osteocytes positively enhanced the production of cellular superoxide in vivo. Sod2-deficient femurs showed remarkable bone loss in an age-dependent manner. Sod2 deficiency significantly suppressed bone formation and increased bone resorption concomitant with the upregulation of sclerostin and receptor activator of NF-κB ligand (RANKL). These findings demonstrate that the mitochondrial superoxide induced in osteocytes by Sod2 ablation causes age-related bone loss due to the impairment of canalicular networks and bone metabolism via the deregulation of the sclerostin and RANKL expression.

Free Research Field

骨代謝学　整形外科・運動器医学