The regulation of osteocyte function and mechanosignaling via light stimulus

• Project/Area Number: 15K15558
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Osaka Dental University
• Principal Investigator: NOTOMI Takuya 大阪歯科大学, 歯学部, 講師 (70542249)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 骨代謝 / 骨細胞 / 光遺伝学 / 力学的刺激 / 細胞膜電位 / 光操作

Outline of Final Research Achievements

Age-related bone diseases such as osteoporosis are serious problem in an aged society. To prevent these bone diseases, we have done the study of relationships between the changes in membrane potential and bone remodeling. To investigate the relationships between mechanosignaling and the changes in membrane potential, the light-gated ion channels and pump were transfected into osteocyte and their cells were transplanted to calvariae bone. After invivoloading on bone, invivo loading with light stimulus increased bone formation compared to control. In summary, our results indicate that the changes in membrane potential affects the response of bone mechanosignaling.

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
• [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