Role of regulators of calcineurin 1, RCAN1 as an endogenous calcineur in inhibitor, on osteoolast differentiation

• Project/Area Number: 20791366
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Aichi Gakuin University
• Principal Investigator: OBATA Koji Aichi Gakuin University, 医学部, 助教 (40378229)
• Research Collaborator: 高木 都 奈良県立医科大学, 医学部・第二生理学, 教授 (00033358) ; ZHANG Guo-Xing 奈良県立医科大学, 医学部・第二生理学, 助教 (90444728) ; 松吉 ひろ子 奈良県立医科大学, 医学部・第二生理学, 助教 (10448772) ; 横田 充弘 愛知学院大学, 歯学部, 客員教授 (50201851)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 骨代謝 / シグナル伝達 / 破骨細胞 / カルシウム / カルシニューリン / 骨吸収 / RCAN / RCAN1 / NFAT / RAW264.7 / siRNA / 遺伝子導入 / 可溶性RANKL

Research Abstract

破骨細胞分化誘導過程においてRCANのmRNA発現が、分化が進むに従い、増大することを見出した。機能抑制実験では、予想に反して破骨細胞形成への影響はほとんど見られないため、RCANファミリーであるRCAN2および3の代償機構が働いている可能性を示した。一方、破骨形成分化過程において、交感神経系のα1-アドレナリン受容体の発現が増加していること、α-作動薬は破骨細胞の細胞内カルシウム濃度の上昇を引き起こすことを見出した。本研究によりRCAN1は、交感神経による骨代謝にも重要な役割を持つことが考えられる。

Research Products

• [Journal Article] A 5-HT(4)-receptor activation-induced neural plasticity enhances in vivo reconstructs of enteric nerve circuit insult (2010)
  • Author(s): Matsuyoshi H, Kuniyasu H, Okumura M, Misawa H, Katsui R, Zhang GX, Obata K, Takaki M
  • Journal Title: Neurogastroenterol Motil (in press)
  • Peer Reviewed
• [Journal Article] Cardioprotective effects of a novel calpain inhibitor SNJ-1945 for reperfusion injury after cardioplegic cardiac arrest (2010)
  • Author(s): Yoshikawa Y, Zhang GX, Obata K, Ohga Y, Matsuyoshi H, Taniguchi S, Takaki M
  • Journal Title: Am J Physiol Heart Circ Physiol 298(2)
  • Peer Reviewed
• [Journal Article] Inhibition of cytochrome c release by 10-N-nonyl acridine orange, a cardiolipin-specific dye, during myocardial ischemia-reperfusion in the rat (2010)
  • Author(s): Zhang GX, Kimura S, Murao K, Obata K, Matsuyoshi H, Takaki M
  • Journal Title: Am J Physiol Heart Circ Physiol 298(2)
  • Peer Reviewed
• [Journal Article] Inhibition of cytochrome c release by 10-N-nonyl acridine orange, acardiolipin-specific dye, during myocardial ischemia-reperfusion in the rat. (2010)
  • Author(s): Zhang GX, et al.
  • Journal Title: Am J Physiol Heart Circ Physiol. 298(2)
  • Peer Reviewed
• [Journal Article] Left ventricular function of isoproterenol-induced hypertrophied rat hearts perfused with blood: mechanical work and energetics (2009)
  • Author(s): Nakajima-Takenaka C, Zhang GX, Obata K, Tohne K, Matsuyoshi H, Nagai Y, Nishiyama A, Takaki M
  • Journal Title: Am J Physiol Heart Circ Physiol 297(5)
  • Peer Reviewed
• [Journal Article] Mechanism of diastolic stiffening of the failing myocardium and its prevention by angiotensin receptor and calcium channel blockers (2009)
  • Author(s): Cheng XW, Okumura K, Kuzuya M, Jin Z, Nagata K, Obata K, Inoue A, Hirashiki A, Takeshita K, Unno K, Harada K, Shi GP, Yokota M, Murohara T
  • Journal Title: J Cardiovasc Pharmacol Pages: 47-56
  • Peer Reviewed
• [Journal Article] Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats (2009)
  • Author(s): Yamada T, Nagata K, Cheng XW, Obata K, Saka M, Miyachi M, Naruse K, Nishizawa T, Noda A, Izawa H, Kuzuya M, Okumura K, Murohara T Yokota M
  • Journal Title: Eur J Pharmacol 615(1-3) Pages: 163-70
  • Peer Reviewed
• [Journal Article] Long-term administration of nifedipine attenuates cardiac remodeling and diastolic heart failure in hypertensive rats. (2009)
  • Author(s): Yamada T, et al.
  • Journal Title: J Cardiovasc Pharmacol. 615(1-3) Pages: 163-170
  • Peer Reviewed
• [Journal Article] Left ventricular function of isoproterenol-induced hypertrophied rathearts perfused with blood : mechanical work and energetics. (2009)
  • Author(s): Nakajima-Takenaka C, et al.
  • Journal Title: Am J Physiol Heart Circ Physiol.2 97(5)
  • Peer Reviewed
• [Journal Article] 骨関連細胞と神経細胞の共培養実験法の確立と細胞間相互作用の検討 (2008)
  • Author(s): 小畑孝二, 戸苅彰史
  • Journal Title: 口腔組織培養学会誌 17: Pages: 15-25
• [Journal Article] Dobutamine stress testing as a diagnostic tool for evaluation of myocardial contractile reserve in asymptomatic or mildly symptomatic patients with dilated cardiomyopathy (2008)
  • Author(s): Kobayashi M, Izawa H, Cheng XW, Asano H, Hirashiki A, Unno K, Ohshima S, Yamada T, Murate Y, Kato TS, Obata K, Noda A, Nishizawa T, lsobe S, Nagata K, Matsubara T, Murohara T, Yokota M
  • Journal Title: JACC Cardiovasc Imaging 1 Pages: 718-26
  • Peer Reviewed
• [Journal Article] Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension: role of activation of AMP-activated protein kinase and inhibition of Akt (2008)
  • Author(s): Kato MF, Shibata R, Obata K, Miyachi M, Yazawa H, Tsuboi K, Yamada T, Nishizawa T, Nada A, Cheng XW, Murate T, Koike Y, Murohara T, Yokota M, Nagata K
  • Journal Title: J Hypertens 26(8) Pages: 1669-76
  • Peer Reviewed
• [Journal Article] Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment (2008)
  • Author(s): Cheng XW, Murohara T, Kuzuya M, Izawa H, Sasaki T, Obata K, Nagata K, Nishizawa T, Kobayashi M, Yamada T, Kim W, Sato K, Shi GP, Okumura K, Yokota M
  • Journal Title: Am J Pathol 173(2) Pages: 358-69
  • Peer Reviewed
• [Journal Article] Xanthine oxidase inhibition improves left ventricular dysfunction in dilated cardiomyopathic hamsters (2008)
  • Author(s): Hayashi K, Kimata H, Obata K, Matsushita A, Fukata A, Hashimoto K, Noda A, Iwase M, Koike Y, Yokota M, Nagata K
  • Journal Title: J Card Fail 14(3) Pages: 238-44
  • Peer Reviewed
• [Presentation] Overexpression of calmodulin in cardiomyocytes induces cardiac hypertrophy by a calcineudn-dependet pathway (2009)
  • Author(s): Obta K: Guo-Xing Zhang, Hiroko Matsuyoshi, Mitsuhiro Yokota Miyako Takaki
  • Organizer: 第102回近畿生理学談話会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-13
• [Presentation] Possible mechanisms of AT1 receptor blcckade on β-adrenergic receptor stimulation-induced cardiac hypertrophy (2009)
  • Author(s): Guo-Xing Zhang, Shoji Kimura, Koji Murao, Koji Ohata, Hiroko Matsuyoshi, Miyako Takah
  • Organizer: 第102回近畿生理学談話会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-13
• [Presentation] イソプロテレノール誘導肥大心の左心室心筋スライスのカルシウムトランジェントの変化 (2009)
  • Author(s): 服部宇孜・竹下大輔・張国興・盤二・松吉ひろ子・三澤裕美・高木都
  • Organizer: 第102回近畿生理学談話会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-13
• [Presentation] Overexpression of calmodulin in cardiomyocytes induces cardiachypertrophy by a calcineurin-dependent pathway. (2009)
  • Author(s): Obata K, et al.
  • Organizer: 第102回近畿生理学談話会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-13
• [Presentation] 共培養実験系を用いた神経細胞と骨芽細胞の細胞間相互作用の検討 (2009)
  • Author(s): 小畑孝二、浅田啓嗣、青木久美子、高木都
  • Organizer: 第37回自律神経生理研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-12-05
• [Presentation] Effects of HMG-CoA reductase inhibitor, pitavastatin on cardiac function and survival in a rat model of hypertensive heart failure. BBSRC Japan Partnering Programme 2007-2011 (2009)
  • Author(s): Obata K
  • Organizer: The 36th International Congress of Physiological Science. Satellite Symposium #8
  • Place of Presentation: In Benesse Art Site Naoshima. Kagawa
• [Presentation] 共培養実験系を用いた神経細胞と破骨細胞の細胞間相互作用の検討 (2009)
  • Author(s): 小畑孝二、須賀智子、後藤滋巳、戸苅彰史
  • Organizer: 第82回日本薬理学会
  • Place of Presentation: 横浜
• [Presentation] 破骨細胞と神経細胞の共培養実験法の確立と細胞間相互作用の検討 (2008)
  • Author(s): 小畑孝二、戸苅彰史
  • Organizer: 第45回口腔組織培養学会
  • Place of Presentation: 松本
  • Year and Date: 2008-11-15
• [Presentation] Direct Neurite-osteoclastic Cell Communication in Co-culture System (2008)
  • Author(s): Koji. Obata, Satoko Suga, Shigemi Goto, Akifumi Togari
  • Organizer: 第56回国際歯科研究学会日本部会学術大会
  • Place of Presentation: 名古屋
• [Presentation] 共培養実験系における骨芽細胞と神経細胞の機能的相互作用 (2008)
  • Author(s): 小畑孝二、近藤久貴、新井通次、戸苅彰史
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
• [Presentation] 共培養実験系における神経細胞と破骨細胞の相互作用 (2008)
  • Author(s): 須賀智子、小畑孝二、古野忠秀、近藤久貴、新井通次、中西守、後藤滋巳、戸苅彰史
  • Organizer: 第50回歯科基礎医学会学術大会
  • Place of Presentation: 東京
• [Presentation] 骨芽細胞と神経細胞の共培養実験系におけるα-アドレナリン受容体を介した相互作用 (2008)
  • Author(s): 小畑孝二, 戸苅彰史
  • Organizer: 第50回歯科基礎医学会学術大会
  • Place of Presentation: 東京