The role of oxidative stress in the maintenance of bone metabolism
| Project/Area Number |
24791568
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NOJIRI Hidetoshi 順天堂大学, 整形外科, 助教 (10317456)
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| 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)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 酸化ストレス / 骨粗鬆症 / 骨細胞 / Mn-SOD / 骨芽細胞 / 破骨細胞 / 加齢 / 骨代謝 |
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| 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.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Mitochondrial superoxide in osteocytes perturbs canalicular networks in the setting of age-related osteoporosis.2015
Author(s)
Kobayashi K1, Nojiri H2, Saita Y2, Morikawa D1, Ozawa Y3, Watanabe K3, Koike M1, Asou Y4, Shirasawa T5, Yokote K6, Kaneko K2, Shimizu T3.
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Journal Title
Scientific Reports
Volume: Mar 16;5
Issue: 1
Pages: 9148-9148
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cytoplasmic reactive oxygen species and SOD1 regulate bone mass during mechanical unloading.2013
Author(s)
Morikawa D, Nojiri H, Saita Y, Kobayashi K, Watanabe K, Ozawa Y, Koike M, Asou Y, Takaku T, Kaneko K, Shimizu T.
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Journal Title
J Bone Miner Res
Volume: november 28(11)
Issue: 11
Pages: 2368-80
DOI
Related Report
Peer Reviewed
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[Presentation] SOD2 deficiency in chondrocytes accelerates age-related osteoarthritis in mice2014
Author(s)
M. Koike, H. Nojiri, Y. Ozawa, K. Watanabe, I. Masuda, Y. Muramatsu, H. Kaneko, D. Morikawa, K. Kobayashi, Y. Saita, T. Sasho, T. Shirasawa, K. Yokote, K. Kaneko, T. Shimizu
Organizer
Osteoarthritis and Cartilage 2014 World Congress
Place of Presentation
Paris, France
Year and Date
2014-04-24 – 2014-04-27
Related Report
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[Presentation] Osteocyte Specific Deletion of Superoxide Dismutase2 Induces Osteocyte Loss Resulting in Bone Loss Associated with Impairment of Bone Remodeling2013
Author(s)
Keiji Kobayashi, Hidetoshi Nojiri, Yoshitomo Saita, Daichi Morikawa, Masato Koike, Yusuke Ozawa, Yoshinori Asou, Kazuo Kaneko, Takahiko Shimizu,
Organizer
2013 ASBMR Annual Meeting Abstracts
Place of Presentation
Baltimore, USA
Related Report
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