Inflammatory and necrotic effects of nitrogen-containing bisphosphonates: involvement of phosphate transporters
| Project/Area Number |
16K11672
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Tohoku University |
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Principal Investigator |
Endo Yasuo 東北大学, 歯学研究科, 学術研究員 (50005039)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | bisphosphonate / 炎症 / 顎骨壊死 / etidronate / clodronate / 鎮痛作用 / 副作用 / LPS / IL-1 / bisphosphonte / 骨吸収抑制薬 / リン酸トランスポーター |
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| Outline of Final Research Achievements |
Bisphosphonates (BPs) are widely used anti-bone-resorptive drugs. Among them, the anti-bone-resorptive effects of nitrogen-containing BPs (NBPs) are much stronger than those of non-NBPs. However, NBPs have inflammatory/necrotic side effects, and the osteonecrosis of the jaw induced by NBPs is intractable and serious problem in dentistry. The present study, together with previous studies, demonstrtates that NBPs enter soft-tissue cells via phosphate transporters and non-NBPs inhibit this. These findings suggest that non-NBPs are applicable to treat and prevent the side effects of NBPs. In addition, we found that non-NBPs exhibit analgesic effects, too, via inhibition of neuronal phosphate transporters.
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| Academic Significance and Societal Importance of the Research Achievements |
骨粗鬆症は高齢者の生活低下の大きな原因である．窒素含有bisphosphonates (NBPs) は現在，骨粗鬆症の予防・治療の第一選択薬であり，宇宙での無重力による骨粗鬆の予防薬にも期待されている．しかし残念ながら，NBPsの副作用 (顎骨壊死や発熱などの急性炎症) が大きな問題となっており，その安全な利用法の確立は急務の課題である．臨床成績も含めて私達の研究成果は，NBPsの副作用に対する予防・治療薬として，non-NBPの etidronateとclodronateの有効性を明確に示している．いくつかの方法が報告されているが，有効性は低く，私たちの提案する方法が最善と思われる．
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Report
(5 results)
Research Products
(17 results)
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[Journal Article] Pulmonary platelet accumulation induced by catecholamines: its nvolvement in lipopolysaccharide-induced anaphylaxis-like shock.2017
Author(s)
Zhiqian Yu, Hiroko Saito, Hirotada Otsuka, Yosuke Shikama, Hiromi Funayama, Mai Sakai, Shigeo Murai, Masanori Nakamura, Takashi Yokochi, Haruhiko Takada, Shunji Sugawara, Yasuo Endo.
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Journal Title
International Immunopharmacol
Volume: 43
Pages: 40-53
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Strategy against the Osteonecrosis of the Jaw Associated with Nitrogen-Containing Bisphosphonates (N-BPs): Attempts to Replace N-BPs with the Non-N-BP Etidronate2016
Author(s)
Oizumi T, Yamaguchi K, Sato K, Okada S, Suzuki H, Funayama H, Mori S, Nagasaka H, Tsuchiya M, Hagiwara W, Itoi E, Sugawara S, Takahashi T, Endo Y:
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 39
Issue: 9
Pages: 1549-1554
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Analgesic Effects of 1st Generation Anti-histamines in Mice2016
Author(s)
Mebae Takahashi, Kazuhiro Shima, Masahiro Tsuchiya, Yoshihiro Hagiwara, Hirokazu Mizoguchi, Shinobu Sakurada, Shunji Sugawara, Takuo Fujita, Takeshi Tadano, Makoto Watanabe, Satoshi Fukumoto, Yasuo Endo
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Journal Title
Biological and Pharmaceutical Bulletin
Volume: 39
Issue: 4
Pages: 620-624
DOI
NAID
ISSN
0918-6158, 1347-5215
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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