Functional analysis of membrane proteins whose expression were controlled by NFAT2/NFATc1 in mature osteoclasts

• Project/Area Number: 21791394
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: KITAGAWA Norihiro Nara Institute of Science and Technology, バイオサイエンス研究科, 助教 (30294284)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 破骨細胞 / 骨吸収 / NFATc1 / ITAM / 骨代謝 / NFAT2 / 膜タンパク質 / アクチン / HB-EGF / シグナルシーケンストラップ / ectodomain shedding

Research Abstract

Since NFATc1/NFAT2 is essential for inducing the entire processes of multinucleated cell formation, it seems to be reasonable to speculate that NFATc1 may regulate the expression of membrane proteins which control cell fusion and bone resorption. In this research, we found that 1) HB-EGF suppress osteoblast differentiation through the induction of Twist2 and suppression of nuclear translocation of Smad1, and 2) RADIO acts as a DAP12-associated receptor and is essential for the formation of functional osteoclasts through the regulation of actin-ring formation.

Research Products

• [Journal Article] The 1-Ser analog #290 promotes bone recovery in OP and RA mice. (2011)
  • Author(s): Bahtiar, A., Nakamura, T., Kishida, K., Katsura, J., Nitta, M., Ishida-Kitagawa, N., Ogawa, T., Takeya, T.
  • Journal Title: Phamlacol.Res. in press.
  • Peer Reviewed
• [Journal Article] Purification and identification of lactoperoxidase in milk basic proteins as an inhibitor of osteoclastogenesis. (2011)
  • Author(s): Morita, Y, Ono, A., Serizawa, A., Yogo, K., Ishida-Kitagawa, N., Takeya, T., Ogawa T.
  • Journal Title: J.Dairy Sci. 94 Pages: 2270-9
  • Peer Reviewed
• [Journal Article] Acid sphingomyelinase regulates osteoclastogenesis by modulating sphingosine kinases downstream of RANKL signaling. (2011)
  • Author(s): Bao, X., Ogawa, T., Se, S., Akiyama, M., Bahtiar, A., Takeya, T., Ishida-Kitagawa, N.竹家達夫, 北川(石田)教弘
  • Journal Title: Biochem.Biophys.Res.Commun. 405 Pages: 533-7
  • Peer Reviewed
• [Journal Article] Identification and fUnctional analysis of a new phosphorylation site (Y398) in the SH3 domain of Abi-1. (2011)
  • Author(s): Sato, M., Maruoka, M., Yokota, N., Kuwano, M., Matsui, A., Inada, M., Ogawa, T., Ishida-Kitagawa, N., Takeya, T.小川拓哉, 北川(石田)教弘, 竹家達夫
  • Journal Title: FEBS Lett. 585 Pages: 834-40
  • Peer Reviewed
• [Journal Article] Acid sphingomyelinase regulates osteoclastogenesis by modulating sphingosine kinases downstream of RANKL signaling. (2011)
  • Author(s): Bao, Xilinqiqige
  • Journal Title: Biochemical and biophysical research communications Volume: 405 Pages: 533-7
  • Peer Reviewed
• [Journal Article] 細胞外L-セリンは破骨細胞前駆細胞のアミノ酸栄養シグナル活性化に必須である (2010)
  • Author(s): 小川拓哉, 西田織衣, 的場祐衣, 岸田耕一, 藤井直樹, Anton Bahtiar, 北川(石田)教弘, 竹家達夫
  • Journal Title: アミノ酸研究 4 Pages: 167-9
• [Journal Article] Potential involvement of Twist2 and Erk in the regulation of osteoblastogenesis by HB-EGF-EGFR signaling. (2010)
  • Author(s): Nakamura, T., Toita, H., Yoshimoto, A., Nishimura, D., Takagi, T., Ogawa, T., Takeya, T., Ishida-Kitagawa, N.
  • Journal Title: Cell Struct.Funct. 35 Pages: 53-61
  • Peer Reviewed
• [Journal Article] Potential involvement of Twist2 and Erk in the regulation of osteoblast ogenesis by HB-EGF-EGFR signaling. (2010)
  • Author(s): Takashi Nakamura
  • Journal Title: Cell structure and function Volume: 35 Pages: 53-61
  • Peer Reviewed
• [Journal Article] 細胞外L-セリンは破骨細胞前駆細胞のアミノ酸栄養シグナル活性化に必須である (2010)
  • Author(s): 小川拓哉
  • Journal Title: アミノ酸研究 Volume: 4 Pages: 53-61
• [Journal Article] Potential involvement of Twist2 and Erk in the regulation of osteoblast ogenesis by HB-EGF-EGFR signaling (2010)
  • Author(s): Takashi Nakamura
  • Journal Title: Cell Structure and Function (In press)
  • Peer Reviewed
• [Journal Article] 細胞外L-セリンは破骨細胞分化におけるRANKL-RANKシグナル伝達系活性化に必須である (2009)
  • Author(s): 小川拓哉, 酒井俊樹, 古賀慎太郎, 西田織衣, 的場祐衣, アントンバーティアル, 北川(石田)教弘, 竹家達夫
  • Journal Title: アミノ酸研究 3 Pages: 63-5
• [Journal Article] Identification of a novel L-serine analog that suppresses osteoclastogenesis in vitro and bone turnover in vivo. (2009)
  • Author(s): Bahtiar, A., Matsumoto, T., Nakamura, T., Akiyama, M., Yogo, K., Ishida-Kitagawa, N., Ogawa, T., Takeya, T.北川(石田)教弘, 小川拓哉, 竹家達夫
  • Journal Title: J.Biol.Chem. 284 Pages: 34157-66
  • Peer Reviewed
• [Journal Article] Identification of a novel L-Serine analog that suppresses osteoclastogenesis in vitro and bone turnover in vivo. (2009)
  • Author(s): Anton Bahtiar
  • Journal Title: Journal of Biological chemistry 284 Pages: 34157-34166
  • Peer Reviewed
• [Journal Article] 細胞外L-セリンは破骨細胞分化におけるRANKL-RANKシグナル伝達系活性化に必須である (2009)
  • Author(s): 小川拓哉
  • Journal Title: アミノ酸研究 3 Pages: 63-65
• [Presentation] 骨吸収の異常亢進による骨代謝疾患に対するセリンアナログ#290の投与効果の検討 (2010)
  • Author(s): 桂隼平、Anton Bahtiar、新田麻衣、北川(石田)教弘、小川拓哉、竹家達夫
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-10
• [Presentation] 骨吸収の異常亢進による骨代謝疾患に対するセリンアナログ#290の投与効果の検討 (2010)
  • Author(s): 桂準平
  • Organizer: BMB2010
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2010-12-10
• [Presentation] 破骨細胞における新規アクチン細胞骨格制御因子RADIOの同定と機能解析 (2010)
  • Author(s): 木村貴徳、三浦格、錫林其其格、田中國太郎、北岡良基、北川(石田)教弘
  • Organizer: BMB2010
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] 破骨細胞における新規アクチン細胞骨格制御因子RADIOの同定と機能解析 (2010)
  • Author(s): 木村貴徳
  • Organizer: BMB2010
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2010-12-09
• [Presentation] Identification and Functional Analysis of a Novel Regulator of Actin-ring Formation in Osteoclast. (2010)
  • Author(s): Norihiro Ishida-Kitagawa, Bao Xilinqiqige, Kunitaro Tanaka, Takanori Kimura, Tadashi Miura, Yoshiki Kitaoka, Takuya Ogawa, Tatsuo Takeya
  • Organizer: 32nd Annual Meeting of The ASBMR
  • Place of Presentation: Toronto
  • Year and Date: 2010-10-18
• [Presentation] Identification and Functional Analysis of a Novel Regulator of Actin-ring Formation in Osteoclast. (2010)
  • Author(s): Norihiro Ishida-Kitagawa
  • Organizer: 32nd Annual Meeting of The American Society for Bone and Mineral Research
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2010-10-18
• [Presentation] 破骨細胞における膜タンパク質の網羅的解析と新規アクチン細胞骨格制御因子の同定 (2010)
  • Author(s): 北川(石田)教弘、小川拓哉、竹家達夫
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] 破骨細胞における膜タンパク質の網羅的解析と新規アクチン細胞骨格制御因子の同定 (2010)
  • Author(s): 北川(石田)教弘
  • Organizer: 第28回日本骨代謝学会学術集会
  • Place of Presentation: 東京都新宿区
  • Year and Date: 2010-07-21
• [Presentation] 破骨細胞における膜タンパク質の網羅的解析と新規アクチン細胞骨格制御因子の同定 (2009)
  • Author(s): 田中國太郎、北岡良基、木村貴徳、三浦格、北川(石田)教弘
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] Screening of Membrane Proteins Expressed in Osteoclasts and Identification of a Novel Regulator of the Actin-ring Formation. (2009)
  • Author(s): 田幅太郎
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11