Elucidation of the pathogenesis of bone diseases mediated by osteocyte-sensory nerve networks
Project/Area Number |
17H05104
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Pathobiological dentistry/Dental radiology
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Research Institution | The University of Tokushima |
Principal Investigator |
HIASA Masahiro 徳島大学, 大学院医歯薬学研究部(歯学域), 講師 (90511337)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
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Keywords | がん / 骨細胞 / 感覚神経 / 痛み / 骨痛 / がんと骨病変 / 神経 / Cx43 / 癌 |
Outline of Final Research Achievements |
The purpose of this study was to elucidate the role of crosstalk between osteocytes and sensory nerves via gap junctions in the pathogenesis of bone pain associated with bone metastatic tumor and in bone dysbolism disease. In addition, we have developed clinical applications for bone pain relief and therapeutic agents for bone lesions. The results of this study revealed that osteocytes develop intimate physical contact with sensory neurons in bone, and transfer small molecules via Cx43 to excite sensory neurons and evoke bone pain, indicating a novel pain-modulating function of osteocytes. The communication between osteocytes and sensory neurons may provide a new potential target for treating bone pain.
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Academic Significance and Societal Importance of the Research Achievements |
骨痛は既存の鎮痛薬が効かず苦慮する事例をしばしば認め確立された鎮痛法も乏しい。そのため、より良い治療には骨痛で起こる感覚神経の病的興奮の分子メカニズムを解明することが必要であるが未だ不明な点が多い。本研究は骨組織で大多数を占めメカノセンサーとして働く骨細胞が、骨内を走行する感覚神経とCx43ギャップ結合を介したネットワークを構築し、互いに機能制御を行うことを明らかとした。また、骨細胞をターゲットとした鎮痛法が臨床応用できる可能性を示した。
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Report
(5 results)
Research Products
(56 results)
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[Journal Article] The Roles of ROS Generation in RANKL-Induced Osteoclastogenesis: Suppressive Effects of Febuxostat.2020
Author(s)
1. Ashtar M, Tenshin H, Teramachi J, Bat-Erdene A, Hiasa M, Oda A, Tanimoto K, Shimizu S, Higa Y, Harada T, Oura M, Sogabe K, Nakamura S, Fujii S, Sumitani R, Miki H, Udaka K, Takahashi M, Kagawa K, Endo I, Tanaka E, Matsumoto T, Abe M.
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Journal Title
Cancers (Basel)
Volume: 12
Issue: 4
Pages: 929-929
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] TAK1 is a pivotal therapeutic target for tumor progression and bone destruction in myeloma.2020
Author(s)
2. Teramachi J, Tenshin H, Hiasa M, Oda A, Bat-Erdene A, Harada T, Nakamura S, Ashtar M, Shimizu S, Iwasa M, Sogabe K, Oura M, Fujii S, Kagawa K, Miki H, Endo I, Haneji T, Matsumoto T, Abe M.
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Journal Title
Haematologica
Volume: haematol.2019
Issue: 5
Pages: 1401-1413
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Persistent activation of calcium-sensing receptor suppresses bone turnover, increases microcracks and decreases bone strength2019
Author(s)
Bingzi Dong, Itsuro Endo, Yukiyo Ohnishi, Yukari Mitsui, Kiyoe Kurahashi, Mai Kanai, Masahiro Hiasa, Jumpei Teramachi, Hirofumi Tenshin, Seiji Fukumoto, Masahiro Abe, Toshio Matsumoto.
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Journal Title
JBMR Plus
Volume: inpress
Issue: 7
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effective impairment of myeloma cells and their progenitors by hyperthermia.2018
Author(s)
Hirokazu Miki, Shingen Nakamura, Asuka Oda, Hirofumi Tenshin, Jumpei Teramachi, M. Hiasa, A. Bat-Erdene, Y. Maeda, M. Oura, M. Takahashi, M. Iwasa, T. Harada, S. Fujii, K. Kurahashi, S. Yoshida, K. Kagawa, I. Endo, K. Aihara, M. Ikuo, K. Itoh, Koichiro Hayashi, Michihiro Nakamura, Masahiro Abe
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Journal Title
Oncotarget
Volume: 9
Issue: 12
Pages: 10307-10316
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim inhibiting activity.2018
Author(s)
Fujii S, Nakamura S, Oda A, Miki H, Tenshin H, Teramachi J, Hiasa M, Bat-Erdene A, Maeda Y, Oura M, Takahashi M, Iwasa M, Endo I, Yoshida S, Aihara KI, Kurahashi K, Harada T, Kagawa K, Nakao M, Sano S, Abe M.
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Journal Title
British Journal of Haematology
Volume: 180(2)
Issue: 2
Pages: 246-258
DOI
Related Report
Peer Reviewed
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[Journal Article] Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging2017
Author(s)
Davis HM, Pacheco-Costa R, Atkinson EG, Brun LR, Gortazar AR, Harris J, Hiasa M, Bolarinwa SA, Yoneda T, Ivan M, Bruzzaniti A, Bellido T, Plotkin LI.
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Journal Title
Aging Cell
Volume: 16(3)
Issue: 3
Pages: 551-563
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Versatile anti-myeloma effects by elotuzumab: impact on gamma delta T cells and osteoclasts2020
Author(s)
T Harada, Y Inoue, H Tenshin, A Oda, M Oura, K Sogabe, R Sumitani, S Fujii, S Nakamura, H Miki, K Kagawa, M Hiasa, J Teramachi, M Abe
Organizer
第82回日本血液学会学術集会
Related Report
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[Presentation] Novel therapeutic rationale for targeting HDAC1 and PIM2 in multiple myeloma2019
Author(s)
Takeshi Harada, Asuka Oda, Hiroto Ohguchi, Yohann Grondin, Hirofumi Tenshin, Masahiro Hiasa, Jumpei Teramachi, Masahiro Oura, Kimiko Sogabe, Shiroh Fujii, Shingen Nakamura, Hirokazu Miki, Hirokazu Miki, Kumiko Kagawa, Shuji Ozaki, Teru Hideshima, Kenneth C. Anderson and Masahiro Abe
Organizer
61th ASH Annual Meeting & Exposition
Related Report
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[Presentation] The role of NLRP3 inflammasome activation in joint inflammation and destruction in rheumatoid arthritis: novel therapeutic approaches with TAK1 inhibition2019
Author(s)
Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Asuka Oda, Ashtar Mohannad, Kotaro Tanimoto, Soh Shimizu, Takeshi Harada, Masahiro Oura, Kimiko Sogabe, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe
Organizer
29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting
Related Report
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[Presentation] A progressive auto-amplification loop in TAK1 expression and activation in MM cells2019
Author(s)
Jumpei Teramachi, Shimizu So, Hirofumi Tenshin, Bat-Erdene Ariunzaya, Masahiro Hiasa, Oda Asuka, Takeshi Harada, Ashter Mohannad, Kotaro Tanimoto, Itsuro Endo, Toshio Matsumoto, Eiji Tanaka and Masahiro Abe
Organizer
American Society for Bone and Mineral Society Annual meeting 2019
Related Report
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[Presentation] TAK1 inhibition effectively alleviates joint inflammation as well as bone destruction in rheumatoid arthritis: Suppression of NLRP3 inflammasome-mediated inflammation and osteoclastic bone resorption2019
Author(s)
Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Asuka Oda, Ashtar Mohannad, Kotaro Tanimoto, Masami Iwasa, Bat-Erdene Ariunzaya, Takeshi Harada, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto and Masahiro Abe
Organizer
American Society for Bone and Mineral Society Annual meeting 2019
Related Report
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[Presentation] TAK1阻害は関節リウマチにおけるNLRP3インフラマソーム誘導性の炎症および骨破壊を抑制する2019
Author(s)
天眞 寛文, 寺町 順平, 日浅 雅博, 谷本 幸多朗, ASHTAR MOHANNAD, Ariunzaya Bat-Erdene, 岩佐 昌美, 原田 武志, 中村 信元, 三木 浩和, 遠藤 逸朗, 田中 栄二, 松本 俊夫, 安倍 正博
Organizer
第37回日本骨代謝学会学術集会
Related Report
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[Presentation] IFN-gamma and ATRA cooperatively upregulates CD38 in myeloma cells: critical contribution of IRF1 and HDAC6.2018
Author(s)
Ariunzaya Bat-Erdene, Takeshi Harada, Masami Iwasa, Asuka Oda, Shiro Fujii, Kimiko Sogabe, Shingen Nakamura, Jumpei Teramachi, Masahiro Hiasa, Hirofumi Tenshin, Mohannad Ashtar, Koutarou Tanimoto, Hirokazu Miki, Mamiko Takahashi, Masahiro Oura, Kumiko Kagawa, Masahiro Abe
Organizer
第80回日本血液学会学術集会
Related Report
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[Presentation] Opposite effects of TRAIL on the Sp1-c-FLIP survival pathway in myeloma cells and osteoclasts.2018
Author(s)
Hirofumi Tenshin, Jumpei Teramachi, Masahiro Hiasa, Asuka Oda, Mohannad Ashtar, Kotaro Tanimoto, Iwasa Masami, Ariunzaya Bat-Erdene, Takeshi Harada, Shingen Nakamura, Hirokazu Miki, Itsuro Endo, Eiji Tanaka, Toshio Matsumoto, Masahiro Abe
Organizer
ASBMR 2018 Annual meeting
Related Report
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