Development of a new drug candidate to stimulate bone formation by oligomerization of RANKL-binding peptides
Project/Area Number |
25293377
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Functional basic dentistry
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
AOKI Kazuhiro 東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (40272603)
|
Co-Investigator(Kenkyū-buntansha) |
HONMA Masashi 東京大学, 医学部附属病院, 准教授 (60401072)
|
Co-Investigator(Renkei-kenkyūsha) |
YOSHIOKA Yasuo 大阪大学, 大阪大学微生物病研究所, 准教授 (00392308)
UDAGAWA Nobuyuki 松本歯科大学, 歯学部, 教授 (70245801)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
|
Keywords | 新規骨形成薬 / RANKL結合ペプチド / BMP-2 / CHPナノゲル / ゼラチンハイドロゲル / ペプチド修飾 / 注射による骨造成 / 粒子状担体 / 骨形成 / 粘膜下注射 / 骨造成 / 低侵襲 / 骨形成促進剤 / ペプチド創薬 / 骨芽細胞 / RANKL親和性 / 骨形態計測 / リボゾーム化 |
Outline of Final Research Achievements |
We have continuously been studying the stimulatory effects of peptide drugs on bone formation, which are known to be able to be fully synthesized, instead of developing the antibody-drugs. Two problems need to be clarified for developing the peptide drugs toward clinical applications; 1.the effective dose should be low, 2. the drug effects should be stable. This time, we have performed a peptide screening and obtained drug candidates with higher affinity to RANKL, which could have a stimulatory effects of bone formation at a lower dose. Next, we showed the stable bone formation of the RANKL-binding peptide when used with BMP-2. The third, we have developed appropriate carriers of peptide drugs for inducing bone formation, especially when we used the granular type of gelatin hydrogel carrier, we could obtain the stable bone formation at the site of injection of the peptide with BMP-2.
|
Report
(4 results)
Research Products
(60 results)
-
-
-
[Journal Article] The inhibitory effects of a RANKL-binding peptide on articular and periarticular bone loss in a murine model of collagen-induced arthritis: A bone histomorphometric study.2015
Author(s)
Kato G, Shimizu Y, Arai Y, Suzuki N, Sugamori Y, Maeda M, Takahashi M, Tamura Y, Wakabayashi N, Murali R, Ono T, Ohya K, Mise-Omata S, Aoki K.
-
Journal Title
Arthritis Research & Therapy
Volume: Sep 12
Issue: 1
Pages: 251-264
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged1aDepartment of Immunology.2014
Author(s)
Negishi, N. Suzuki, D. Ito, R. Irie, N. Matsuo, K. Yahata, T. Nagano, K. Aoki, K. Ohya, K. Hozumi, K. Ando, K. Tamaoki, N. Ito, M. Habu, S.
-
Journal Title
Experimental Hematology
Volume: 42
Pages: 487-494
Related Report
-
[Journal Article] The p65 subunit of NF-κB suppresses BMP2-induced bone formation by inhibiting Smad DNA binding via an interaction with Smad42014
Author(s)
Hirata-Tsuchiya S, Fukushima H, Katagiri T, Ohte S, Shin M, Nagano K, Aoki K, Morotomi T, Sugiyama G, Doi T, Takeuchi H, Ohya K, Terashita M, Hirata M, Kitamura C, Jimi E.
-
Journal Title
Mol Endocrinol
Volume: 28
Issue: 9
Pages: 1460-1470
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
-
-
-
-
[Journal Article] The local administration of TNF-α; and RANKL antagonist peptide promotes BMP-2-induced bone formation.2013
Author(s)
Khan, M. Alles, N. Soysa, N. Mamun, A. Nagano, K. Mikami, R. Furuya, Y. Yasuda, H. Ohya, K. Aoki, K
-
Journal Title
J Oral Biosciences
Volume: 55
Issue: 1
Pages: 47-54
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Stimulation of bone formation in cortical bone of mice treated with a receptor activator of nuclear factor-κB ligand (RANKL)-binding peptide that possesses osteoclastogenesis inhibitory activity.2013
Author(s)
Furuya Y, Inagaki A, Khan M, Mori K, Penninger JM, Nakamura M, Udagawa N, Aoki K, Ohya K, Uchida K, Yasuda H
-
Journal Title
J Biol Chem
Volume: 288
Issue: 8
Pages: 5562-5571
DOI
Related Report
Peer Reviewed
-
[Journal Article] p130Cas plays important roles in osteoclastic bone resorption2013
Author(s)
Nagai Y, Osawa k, Fukushima H, Tamura Y, Aoki K, Ohya K, Yasuda H, Hikiji H, Kato S, Honda H, Nakamura I, Maki K, Jimi E
-
Journal Title
J. Bone Miner. Res
Volume: 28
Issue: 12
Pages: 2449-2462
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Disruption of NF-κB1 prevents bone loss caused by mechanical unloading.2013
Author(s)
Nakamura H, Aoki K, Masuda W, Alles N, Nagano K, Fukushima H, Osawa K, Yasuda H, Nakamura I, Mikuni-Takagaki Y, Ohya K, Maki K, Jimi E.
-
Journal Title
J Bone Miner Res.
Volume: 28
Issue: 6
Pages: 1457-1467
DOI
NAID
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
[Presentation] A RANKL-binding peptide accelerates BMP-induced bone regeneration in murine maxilla by subperiosteal injections.2015
Author(s)
Uehara T, Mise S, Arai Y, Sugamori Y, Kato G, Tamura Y, Tabata Y, Murali R, Wakabayashi N, Miyashin M, Aoki K
Organizer
13th Congress of the Internatitonal Society of Bone Morphometry
Place of Presentation
東京ガーデンパレス(東京都文京区)
Year and Date
2015-04-27
Related Report
Int'l Joint Research
-
-
-
-
-
[Presentation] RANKL-binding peptides increased bone formation in a murine calvarial defect model.2014
Author(s)
Y, Sugamori. M, Honma. G, Kato. Y, Tamura. Y, Furuya. H, Yasuda. Y, Tabata. N, Udagawa. K, Ohya. H, Suzuki. K, Aoki.
Organizer
アメリカ骨代謝学会2014
Place of Presentation
テキサス州ヒューストン市(USA)
Year and Date
2014-09-12 – 2014-09-15
Related Report
-
-
[Presentation] Basic analysis for screening a novel bone-regenerating peptide from the phage peptide library.2014
Author(s)
Nagano, T. Mukai, Y. Sugamori, Y. Kato, G. Ohya, K. Aoki, K. Higashisaka, K. Yasuo Yoshioka, Y. Nagano, K. Kamada, H. Tsunoda, S. Tsutsumi, Y.
Organizer
CRS2014
Place of Presentation
シカゴ市(USA)
Year and Date
2014-07-12 – 2014-07-16
Related Report
-
-
-
-
-
-
-
[Presentation] An Osteoprotegerin-like Peptide Inhibits Bone Loss in Collagen Type II-Induced Murine Arthritis.2013
Author(s)
Kato, G. Maeda, M. Alles, N. Mamun, A. Khan, M. Sugamori, Y. Takahashi, M. Tamura, Y. Murali, R. Ohya, K. Aoki, K.
Organizer
IBMS/JSBMR第2回合同国際会議
Place of Presentation
神戸市/神戸コンベンションセンター・神戸ポートピアホテル
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-