| Project/Area Number |
14207056
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NODA Masaki Tokyo Medical and Dental University, Medical Research Institute, Molecular Pharmacology, Professor, 難治疾患研究所, 教授 (50231725)
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| Co-Investigator(Kenkyū-buntansha) |
NIFUJI Akira Tokyo Medical and Dental University, 先端遺伝子発現研究センター, 研究員 (00240747)
TSUJI Kunikazu Tokyo Medical and Dental University, Medical Research Institute, Molecular Pharmacology, 難治疾患研究所, 助手 (20323694)
INOUE Keiichi Tokyo Medical and Dental University, Medical Research Institute, Molecular Pharmacology, 難治疾患研究所, 助手 (30396981)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥43,160,000 (Direct Cost: ¥33,200,000、Indirect Cost: ¥9,960,000)
Fiscal Year 2005: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Fiscal Year 2004: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2003: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2002: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
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| Keywords | osteoblast / osteoclast / osteoporosis / bone formation / bone resumption / transcriptionfactor / cartilage / stem cell / 骨量 / 交感神経系 / βブロッカー / 骨折 / 閉経後骨粗鬆症 / Tob / ノックアウトマウス / 卵巣摘除 / エストロジェン / 副甲状腺ホルモン / オステオポンチン / マトリックス / 骨塩量 / 海綿骨 / 外骨膜 / 骨形成速度 / 石灰化速度 / BMP / 低骨量状態 / Smad |
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| Research Abstract |
This research program has been aimed to understand the mechanisms for the bone formation and bone resumption to be contributing to contemplate measures for the regeneration of bone to treat the patients suffering from osteoporosis or the large bone defects. For this program we have main three purposes. The first one is to understand the mechanisms of osteoblastic differentiation. The second project purpose is to analyze the molecular cascade for differentiation of osteoclasts. The third research aim is to elucidate mechanisms underlying the cartilage destruction and bone destruction. The first purpose, we have revealed that CIZ is acting as antagonist against BMP actions. Furthermore, osteoblastic activity as well as osteoclastic activities are under the control of sympathetic nerves tone. These molecular regulations also lead to suppression of osteoblastic transcription factors such as Runx2. In addition, other molecules such as BMP antagonist, Sost as well as HLH proteins, have been shown to work together to modulate the function of osteoblasts.
For the second purpose, we analyze the molecules which are contributing to osteoclast differentiation and have shown that osteopontin as well as Klotho proteins are involved in the regulation of osteoclastic activities, Klotho protein interacts with osteoprotegrins. Bone resorption results in osteopenia. However, at the same time suppression of bone formation by Tob which also is contributing to such reduction of bone mass during the differentiation of osteoblasts. MIT-F was identified to be involved in the regulation of osteoclastic differentiation.
For the third purpose, we have shown that degradation of cartilage layers in the rehumatoidarthritis models could be mediated by OPN. We have also analyze the function of transcription factor, Sox9 and identified stem cells in tendons. These three research activities altogether contributed to understanding of bone and cartilage development and regeneration.
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