Investigation into the mechanism of mechano-transduction via neurotransmitter receptors and ion channels

• Project/Area Number: 23791626
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NOTOMI Takuya 東京医科歯科大学, 歯と骨のGCOE拠点, 特任講師 (70542249)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 膜電位 / 骨代謝 / 破骨細胞 / イオンチャネル

Research Abstract

Bone diseases are serious problem in an aged society and their treatment is necessary for maintaining QOL. To prevent bone diseases, we have done the study of effects of ion channels and membrane potential in bone. To investigate the signaling mechanism via ion channel and receptor, we examined the function of bone cells by light-sensitive ion channel and pump. The light-gated ion channels and pump were transfected into bone cells and then the role of membrane potential on those cells were investigated. Further, based on their results, we identified bone remodeling-related novel ion channels. In summary, our results indicate that membrane potential regulate bone cell function and bone remodeling-related novel ion channels are important for osteoclastic functions.

Research Products

• [Journal Article] Osteoblastic differentiation enhances expression of TRPV4 that is required for calcium oscillation induced by mechanical force (2013)
  • Author(s): Takafumi Suzuki, Takuya Notomi (Corresponding author), Daizuke Miyajima, Fumitaka Mizoguchi, Tadayoshi Hayata, Tetsuya Nakamoto, Ryo Hanyu, Paksinee Kamolratanakul, Atsuko Mizuno, Makoto Suzuki, Yoichi Ezura, Yuichi Izumi, Masaki Noda
  • Journal Title: Bone Volume: 54(1) Pages: 172-8
• [Journal Article] Nck1 deficiency accelerates unloading-induced bone loss (2013)
  • Author(s): Aryal Smiriti, Kentaro Miyai, Yoichi Ezura, Tadayoshi Hayata, Takuya Notomi, Tetsuya Nakamoto, Tony Pawson, Masaki Noda
  • Journal Title: J. Cell. Physiol Volume: 228:7 Pages: 1397-1403
• [Journal Article] Osteoblastic differentiation enhances expression of TRPV4 that is required for calcium oscillation induced by mechanical force (2013)
  • Author(s): Takafumi Suzuki
  • Journal Title: Bone Volume: 54(1) Issue: 1 Pages: 172-8
  • DOI: 10.1016/j.bone.2013.01.001
  • Peer Reviewed
• [Journal Article] Nck1 Deficiency Accelerates Unloading-Induced Bone Loss (2013)
  • Author(s): Aryal A. C. S, Miyai K, Hayata T, Notomi T, Nnakamoto T, Pawson T, Ezura Y, Noda M.
  • Journal Title: Journal of Cellular Physiology Volume: 228 Issue: 7 Pages: 1397-403
  • DOI: 10.1002/jcp.24317
  • Peer Reviewed
• [Journal Article] Identification of two pore channel 2 as a novel regulator of osteoclastogenesis (2012)
  • Author(s): Takuya Notomi (Corresponding author),Yoichi Ezura, Masaki Noda
  • Journal Title: J. Biol. Chem. Volume: 287(42) Pages: 35057-64
• [Journal Article] Profilin1 regulates sternum development and endochondral bone formation. (2012)
  • Author(s): Daisuke Miyajima, Tadayoshi Hayata, Takafumi Suzuki, Hiroaki Hemmi, Yoichi Ezura, Tetsuya Nakamoto, Takuya Notomi, Teruo Amagasa, Ralph T Bottcher, Mercedes Costell, Reinhard Fassler, Masaki Noda.
  • Journal Title: J. Biol. Chem. Volume: 287(40) Pages: 33545-53
• [Journal Article] Anabolic action of parathyroid hormone regulated by the beta2-adrenergic receptor. (2012)
  • Author(s): Ryo Hanyu, Vanessa L. Wehbi, Tadayoshi Hayata, Shuichi Moriya, Timothy N. Feinsteind, Yoichi Ezura, Masashi Nagao, Yoshitomo Saita, Hiroaki Hemmi, Takuya Notomi, Tetsuya Nakamoto, Ernestina Schipani, Shu Takeda, Kazuo Kaneko, Hisashi Kurosawa, Gerard Karsenty, Henry M. Kronenberg, Jean-Pierre Vilardaga and Masaki Noda.
  • Journal Title: Proc Natl Acad Sci USA Volume: 109(19) Pages: 7433-7438
• [Journal Article] CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells. (2012)
  • Author(s): Tomomi Sakuma, Tetsuya Nakamoto, Hiroaki Hemmi, Sohei Kitazawa S, Riko Kitazawa, Takuya Notomi, Tadayoshi Hayata, Yoichi Ezura, Teruo Amagasa and Masaki Noda.
  • Journal Title: J Cell Physiol Volume: 227:7 Pages: 2807-2812
• [Journal Article] Identification of two pore channel 2 as a novel regulator of osteoclastogenesis (2012)
  • Author(s): Takuya Notomi
  • Journal Title: Journal of Biological Chemistry Volume: 287(42) Issue: 42 Pages: 35057-64
  • DOI: 10.1074/jbc.m111.328930
  • Peer Reviewed
• [Journal Article] Profilin1 regulates sternum development and endochondral bone formation. (2012)
  • Author(s): Daisuke Miyajima
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 33545-53
  • Peer Reviewed
• [Journal Article] Anabolic action of parathyroid hormone regulated by the beta2-adrenergic receptor (2012)
  • Author(s): Hanyu, R.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 109 Issue: 19 Pages: 7433-7438
  • DOI: 10.1073/pnas.1109036109
  • Peer Reviewed
• [Journal Article] CIZ/NMP4 is expressed in B16 melanoma and forms a positive feedback loop with RANKL to promote migration of the melanoma cells (2012)
  • Author(s): Sakuma, T., Nakamoto, T., Hemmi, H., Kitazawa, S., Kitazawa, R., Notomi, T., Hayata, T., Ezura, Y., Amagasa, T., and Noda, M
  • Journal Title: Journal of cellular physiology Volume: 227 Issue: 7 Pages: 2807-2812
  • DOI: 10.1002/jcp.24066
  • Peer Reviewed
• [Journal Article] Sympathetic control of bone mass regulated by osteopontin. (2011)
  • Author(s): Nagao M, Feinstein TN, Ezura Y, Hayata T, Notomi T, Saita Y, Hanyu R, Hemmi H, Izu Y, Takeda S, Wang K, Rittling S, Nakamoto T, Kaneko K, Kurosawa H, Karsenty G, Denhardt DT et al.,
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 17767-72
  • Peer Reviewed
• [Journal Article] MURF1 deficiency suppresses unloading-induced effects on osteoblasts and osteoclasts to lead to bone loss (2011)
  • Author(s): Kondo H, Ezura Y, Nakamoto T, Hayata T, Notomi T, Sorimachi H, Takeda S, Noda M,
  • Journal Title: J.Cell.Biochem Volume: 112 Pages: 3525-30
  • Peer Reviewed
• [Journal Article] Per-1 is a specific clock gene regulated by parathyroid hormone (PTH) signaling in osteoblasts and is functional for the transcriptional events induced by PTH (2011)
  • Author(s): Hanyu R, Hayata T, Nagao M, Saita Y, Hemmi H, Notomi T, Nakamoto T, Schipani E, Knonenbery H, Kaneko K, Kurosawa H, Ezura Y, Noda M
  • Journal Title: J.Cell.Biochem Volume: 112 Pages: 433-438
  • Peer Reviewed
• [Journal Article] Nanogel-based scaffold delivery of prostaglandin E(2) receptor-specific agonist in combination with a low dose of growth factor heals critical-size bone defects in mice (2011)
  • Author(s): Kamolratanakul P, Hayata T, Ezura Y, Kawamata A, Hayashi C, Yamamoto Y, Hemmi H, Nagao M, Hanyu R, Notomi T, Nakamoto T, Amagasa T, Akiyoshi K, Noda M
  • Journal Title: Arthritis Rheum Volume: 63 Pages: 1021-1033
  • Peer Reviewed
• [Journal Article] Osteopontin deficiency enhances parathyroid hormone/parathyroid hormone related peptide receptor (PPR) signaling-induced alteration in tooth formation and odontoblastic morphology (2011)
  • Author(s): Morishita M, Ono N, Miyai K, Nakagawa T, Hanyu R, Nagao M, Kamolratanakul P, Notomi T, Rittling SR, Denhardt DT, Kronenberg HM, Ezura Y, Hayata T, Nakamoto T, Noda M
  • Journal Title: Tissue Cell Volume: 43 Pages: 196-200
• [Presentation] TPC2, Regulates Osteoclastogenesis via Generation of Intracellular Ca2+ Response and Subsequent NFATc1 Localization: A Novel Mechanism of Osteoclastic Ca2+ Signaling (2012)
  • Author(s): Takuya Notomi, Yoichi Ezura, Masaki Noda, Lysosomal Calcium Channel
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Parathyroid Hormone Stimulates Tob1Expression in Osteoblastic Cells in vitro and in vivo (2012)
  • Author(s): Shuichi Moriya, Tadayoshi Hayata, Jumpei Shirakawa, Tetsuya Nakamoto, Takuya Notomi, Yoichi Ezura, Kazuo Kaneko, Masaki Noda
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] PTH Enhances Mechanical Stress-induced Osteoblast Proliferation in Calvarial Derived Osteoblasts via Up-regulation of CyclinD1 Expression (2012)
  • Author(s): Shirakawa Jumpei, Yoichi Ezura, TakuyaNotomi, Tadayoshi Hayata, Tetsuya Nakamoto, Shuichi Moriya, Ken Omura, Masaki Noda
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Cnot3 (Ccr4-not complex subunit3), a Regulator of mRNA Stability, Regulates Bone Mass and Gene Expression Related to Osteoclast Formation (2012)
  • Author(s): Chiho Watanabe, Masahiro Morita, Yoichi Ezura, Tetsuya Nakamoto, Tadayoshi Hayata, Takuya Notomi, Keiji Moriyama, Tadashi Yamamoto, Masaki Noda
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Identification of Signature Genes Selectively Expressed in Mesenchymal Stem Cells Derived from Synovial Joint Tissues (2012)
  • Author(s): Yoichi Ezura, Tadayoshi Hayata, Tetsuya Nakamoto, Takuya Notomi, Takeshi Muneta, Ichiro Sekiya, Masaki Noda
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Nck, an Actin Cytoskeleton Modulator, Controls Expression of Osteocytic Genes, Phosphate Homeostasis by Regulating FGF23 Expression in Bone and Maintains Bone Mass (2012)
  • Author(s): Smriti Aryal A.C, Kentaro Miyai, Yoichi Ezura, Tadayoshi Hayata, Takuya Notomi, Tetsuya Nakamoto, Tony Pawson, Masaki Noda
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] TGF-β1 Decreases Ift88Expression in Chondrocytic Cell Line ATDC5 (2012)
  • Author(s): Makiri Kawasaki, Tetsuya Nakamoto, Takuya Notomi, Tadayoshi Hayata, Yoichi Ezura, Masaki Noda
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Two Pore Channel2を介したリソソーム由来Ca2+による新たな破骨細胞分化制御機構 (2012)
  • Author(s): 納富拓也、江面陽一、野田政樹
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] 一次繊毛タンパクBbs3は骨代謝に関与する (2012)
  • Author(s): 川崎真希理、中元哲也、納富拓也、早田匡芳、江面陽一、野田政樹
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] 骨量制御の新転写後性分子機構:mRNAdeadenylaseであるCcr4-notcomplex構成因子Cnot3の欠失による高回転型の骨量減少の解析 (2012)
  • Author(s): 渡辺千穂、江面陽一、早田匡芳、中元哲也、納富拓也、森山啓司、野田政樹
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] 骨芽細胞におけるGタンパク質共役型受容体(GPCR)によるRANKL制御の検討 (2012)
  • Author(s): 守屋秀一、早田匡芳、中元哲也、納富拓也、江面陽一、金子和夫、野田政樹
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] ヒト骨髄および滑膜由来間葉系細胞において異なるCpGメチル化を示す遺伝子群の探索と骨軟骨細胞分化の制御に関わる転写因子群の抽出:RUNX2およびRUNX3,D+X5,ALX4遺伝子 (2012)
  • Author(s): 江面陽一、早田匡芳、中元哲也、納富拓也、関谷一郎、宗田大、野田政樹
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] Lysosomal Calcium Channel, TPC2, Regulates Osteoclastogenesis via Generation of Intracellular Ca2+ Response and Subsequent NFATc1 Localization: A Novel Mechanism of Osteoclastic Ca2+ Signaling (2012)
  • Author(s): Takuya Notomi
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Parathyroid Hormone Stimulates Tob1 Expression in Osteoblastic Cells in vitro and in vivo (2012)
  • Author(s): Shuichi Moriya
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Nck, an Actin Cytoskeleton Modulator, Controls Expression of Osteocytic Genes, Phosphate Homeostasis by Regulating FGF 23 Expression in Bone and Maintains Bone Mass (2012)
  • Author(s): Smriti Aryal
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] TGF-β1 Decreases Ift88 Expression in Chondrocytic Cell Line ATDC5 (2012)
  • Author(s): Makiri Kawasaki,
  • Organizer: ASBMR 2012
  • Place of Presentation: Minneapolis, Minnesota, USA
• [Presentation] Two Pore Channel 2を介したリソソーム由来Ca2+による新たな破骨細胞分化制御機構 (2012)
  • Author(s): 納富拓也
  • Organizer: 第30回 日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] 一次繊毛タンパクBbs3は骨代謝に関与する (2012)
  • Author(s): 川崎真希理
  • Organizer: 第30回 日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] mRNA deadenylase であるCcr4-not complex構成因子Cnot3の欠失による高回転型の骨量減少の解析 (2012)
  • Author(s): 渡辺千穂
  • Organizer: 第30回 日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] 骨芽細胞におけるGタンパク質共役型受容体(GPCR)によるRANKL制御の検討 (2012)
  • Author(s): 守屋秀一
  • Organizer: 第30回 日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] ヒト骨髄および滑膜由来間葉系細胞において異なるCpGメチル化を示す遺伝子群の探索と骨軟骨細胞分化の制御に関わる転写因子群の抽出：RUNX2およびRUNX3, D+X5, ALX4遺伝子 (2012)
  • Author(s): 江面陽一
  • Organizer: 第30回 日本骨代謝学会
  • Place of Presentation: 東京
• [Presentation] Opto-functional control of intracellular RANKL transport/secretion in osteoblasts to enhance coupling with osteoclasts based on photo-energy conversion of molecularly-engineered channel-rhodopsin (2011)
  • Author(s): Takuya Notomi, Miyuki Kuno, Yoichi Ezura, Masaki Noda
  • Organizer: ASBMR 2011 Annual Meeting
  • Place of Presentation: San Diego, California, USA
• [Presentation] 光エネルギー変換による任意の時間・空間でのRANKL分泌制御法の確立 -膜電位変動によるRANKL分泌機構 (2011)
  • Author(s): 納富拓也、久野みゆき、江面陽一、野田政樹
  • Organizer: 日本骨代謝学会 2011
  • Place of Presentation: 大阪国際会議場