Exercise related mechanosignling based on nervous system and changes in membrane potential

• Project/Area Number: 26282182
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Sports science
• Research Institution: Osaka Dental University
• Principal Investigator: NOTOMI Takuya 大阪歯科大学, 歯学部, 講師 (70542249)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 骨代謝 / 細胞膜電位 / イオンチャネル / 骨芽細胞 / 破骨細胞 / 光遺伝学 / 力学的刺激 / 運動負荷 / 骨リモデリング / 膜電位

Outline of Final Research Achievements

Age-related bone diseases such as osteoporosis are serious problem in an aged society. Mechanical stress and resistance exercise is useful for preventing bone loss. To investigate the relationships between mechanical stress, nervous system and the changes in membrane potential, we overexpressed light-sensitive ion channel and pump in osteoblasts and osteoclasts and identified the targeting molecules via molecular screening based on membrane potential. In invivo experiments, invivo transfection for light-sensitive molecules and cell transplantation were used for investigating bone remodeling. In summary, our results indicate that changes in membrane potential and the receptor for neuronal transmitter affect bone mehanosignaling.

Research Products

• [Int'l Joint Research] シェフィールド大学(英国)
• [Journal Article] Mice Deficient in CIZ/NMP4 Develop an Attenuated Form of K/BxN-Serum Induced Arthritis. (2016)
  • Author(s): Nakamoto T, Izu Y, Kawasaki M, Notomi T, Hayata T, Noda M, Ezura Y.
  • Journal Title: J Cell Biochem. Volume: 117 Issue: 4 Pages: 970-977
  • DOI: 10.1002/jcb.25382
  • Peer Reviewed / Open Access
• [Journal Article] Membrane depolarization regulates intracellular RANKL transport in non-excitable osteoblasts (2015)
  • Author(s): Notomi T, Kuno M, Ezura Y, Honma M, Ishizuka T, Ohura K, Yao H and Noda M.
  • Journal Title: Bone Volume: 81 Pages: 306-314
  • DOI: 10.1016/j.bone.2015.07.031
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Zinc-induced effects on osteoclastogenesis involve activation of hyperpolarization-activated cyclic nucleotide modulated channels via changes in membrane potential (2015)
  • Author(s): Notomi T, Kuno M, Ohura K, Noda M and Skerry TM
  • Journal Title: J Bone Miner Res Volume: 30 Issue: 9 Pages: 1618-1626
  • DOI: 10.1002/jbmr.2507
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Nck influences preosteoblastic/osteoblastic migration and bone mass (2015)
  • Author(s): Aryal Smriti, Kentaro Miyai, Yayoi Izu, Tadayoshi Hayata, Takuya Notomi, Masaki Noda, Yoichi Ezura
  • Journal Title: Proc Natl Acad Sci USA Volume: 112 Issue: 50 Pages: 15432-7
  • DOI: 10.1073/pnas.1518253112
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] TGF-Beta Suppresses Ift88 Expression in Chondrocytic ATDC5 Cells. (2015)
  • Author(s): Kawasaki, M., Ezura, Y., Hayata, T., Notomi, T., Izu, Y., and Noda, M.
  • Journal Title: Journal of Cellular Physiology Volume: - Issue: 11 Pages: 2788-95
  • DOI: 10.1002/jcp.25005
  • Peer Reviewed / Open Access
• [Journal Article] β2 Adrenergic receptor activation suppresses BMP-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells. (2015)
  • Author(s): Yamada, T., Ezura, Y., Hayata, T., Moriya, S., Shirakawa, J., Notomi, T., Arayal, S., Kawasaki, M., Izu, Y., Harada, K., and Noda, M.
  • Journal Title: Journal of Cellular Biochemistry Volume: 116 Issue: 6 Pages: 1144-52
  • DOI: 10.1002/jcb.25071
  • Peer Reviewed / Open Access
• [Journal Article] PTH regulates β2-adrenergic receptor expression in osteoblast-like MC3T3-E1 cells (2015)
  • Author(s): Shuichi Moriya, Tadayoshi Hayata, Takuya Notomi, Smriti Aryal, Testuya Nakamoto, Yayoi Izu, Makiri Kawasaki, Takayuki Yamada, Jumpei Shirakawa, Kazuo Kaneko, Yoichi Ezura, Masaki Noda
  • Journal Title: J Cell Biochem Volume: 116 Pages: 142-148
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Insulinogenic sucrose + amino acid mixture ingestion immediately after resistance exercise has an anabolic effect on bone compared with non-insulinogenic fructose + amino acid mixture in growing rats (2014)
  • Author(s): Takuya Notomi (Corresponding author), Ikuaki Karasaki, Yuichi Okazaki, Nobukazu Okimoto, Yushi Kato, Kiyoshi Ohura, Masaki Noda, Toshitaka Nakamura, Masashige Suzuki
  • Journal Title: Bone Volume: 65 Pages: 42-48
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Changes in membrane potential regulates RANKL intracellular transport via voltage-gated calcium channels in osteoblasts (2016)
  • Author(s): Takuya Notomi, Miyuki Kuno, Akiko Hiyama, Yoichi Ezura, Kiyoshi Ohura, Masaki Noda
  • Organizer: ASBMR2016
  • Place of Presentation: Georgia World Congress Center (Atlanta, Georgia, USA)
  • Year and Date: 2016-09-16
  • Int'l Joint Research
• [Presentation] Zinc-induced effects on osteoclastogenesis involves activation of HCN channels via changes in membrane potential (2015)
  • Author(s): Takuya Notomi, Miyuki Kuno, Akiko Hiyama, Kiyoshi Ohura, Masaki Noda, Timothy M. Skerry
  • Organizer: ASBMR2015
  • Place of Presentation: ワシントン州、米国
  • Year and Date: 2015-10-11
  • Int'l Joint Research
• [Presentation] Membrane depolarization regulates intracellular RANKL transport in non-excitable osteoblasts (2015)
  • Author(s): Takuya Notomi, Miyuki Kuno, Yoichi Ezura, Kiyoshi Ohura, Masaki Noda
  • Organizer: 13th Congress of the International Society of Bone Morphometry
  • Place of Presentation: 東京、日本
  • Year and Date: 2015-04-28
  • Int'l Joint Research
• [Presentation] TGF-beta impairs cilia morphology via suppression of Ift88 expression in chondrocytic ATDC5 cells (2015)
  • Author(s): Makiri Kawasaki, Tadayoshi Hayata, Tetsuya Nakamoto, Takuya Notomi, Shiichi Moriya, Takayuki Yamada, Yayoi Izu, Yoichi Ezura, Masaki Noda
  • Organizer: 13th Congress of the International Society of Bone Morphometry
  • Place of Presentation: 東京、日本
  • Year and Date: 2015-04-28
  • Int'l Joint Research
• [Presentation] BMP-induced alkaline phosphatase expression in osteoblast-like MC3T3E1 cells is suppressed by β2 adrenergic receptor activation (2015)
  • Author(s): Takayuki Yamada, Yoichi Ezura, Tadayoshi Hayata, Shuichi Moriya, Jumpei Shirakawa, Takuya Notomi, Smriti Aryal, Makiri Kawasaki, Yayoi Izu, Kiyoshi Harada, Masaki Noda
  • Organizer: 13th Congress of the International Society of Bone Morphometry
  • Place of Presentation: 東京、日本
  • Year and Date: 2015-04-28
  • Int'l Joint Research
• [Presentation] Morphological and dynamic analysis of migration linked to FUCCI-indicated cell cycle under the influence of PTH and mechanical flow signals (2015)
  • Author(s): Jumpei Shirakawa, Yoichi Ezura, Shuichi Moriya, Makiri Kawasaki, Takayuki Yamada, Takuya Notomi, Tadayoshi Hayata, Atsushi Miyawaki, Ken Omura, Masaki Noda
  • Organizer: 13th Congress of the International Society of Bone Morphometry
  • Place of Presentation: 東京、日本
  • Year and Date: 2015-04-28
  • Int'l Joint Research
• [Presentation] レジスタンス運動直後のインスリン高刺激性糖摂取は、インスリン低刺激性糖摂取に比べて骨量・骨強度を増大させる (2014)
  • Author(s): 納富拓也、大浦清、野田政樹
  • Organizer: 第56回 歯科基礎医学会
  • Place of Presentation: 福岡県、福岡市、福岡国際会議場
  • Year and Date: 2014-09-26
• [Presentation] スフィンゴシン1リン酸はin vitroの破骨細胞形成系において分化促進する (2014)
  • Author(s): 天野均、納富拓也、大浦清
  • Organizer: 第56回 歯科基礎医学会
  • Place of Presentation: 福岡県、福岡市、福岡国際会議場
  • Year and Date: 2014-09-26
• [Presentation] Insulinogenic sucrose+amino acids mixture ingestion immediately after resistance exercise has an anabolic effect on bone compared with non-insulinogenic fructose+amino acids mixture in growing rats (2014)
  • Author(s): Takuya Notomi, Ikuaki Karasaki, Yuichi Okazaki, Nobukazu Okimoto, Yushi Kato, Kiyoshi Ohura, Masaki Noda, Toshitaka Nakamura, Masashige Suzuki
  • Organizer: ASBMR 2014
  • Place of Presentation: テキサス州、米国
  • Year and Date: 2014-09-13
• [Presentation] Preferentially expressed genes in synovium derived stromal cells include atypical genes not expressed highly in mouse synovium but in embryonic cartilages (2014)
  • Author(s): Yoichi Ezura, Tadayoshi Hayata, Takuya Notomi, Ichiro Sekiya, Masaki Noda
  • Organizer: ASBMR 2014
  • Place of Presentation: テキサス州、米国
  • Year and Date: 2014-09-13
• [Presentation] レジスタンス運動直後のインスリン高刺激性糖（砂糖）＋アミノ酸溶液摂取は、インスリン低刺激性糖（果糖）＋アミノ酸溶液摂取に比べて骨量・骨強度を増大させる (2014)
  • Author(s): 納富拓也、唐崎郁晃、岡崎雄一、沖本信和、加藤雄士、大浦清、野田政樹、中村利孝、鈴木正成
  • Organizer: 第32回 日本骨代謝学会
  • Place of Presentation: 大阪府、大阪市、大阪国際会議場
  • Year and Date: 2014-07-25
• [Presentation] 培養軟骨細胞ATDC5において、TGF-beta1は一次繊毛構成遺伝子Ift88の発現を抑制し、一次繊毛を短縮させる (2014)
  • Author(s): 川崎真希理、早田匡芳、中元哲也、納富拓也、江面陽一、野田政樹
  • Organizer: 第32回 日本骨代謝学会
  • Place of Presentation: 大阪府、大阪市、大阪国際会議場
  • Year and Date: 2014-07-25