Clarification of molecular basis underlying acceleration of bone formation

• Project/Area Number: 23659712
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: IMAI Yuuki 東京大学, 分子細胞生物学研究所, 特任講師 (10423873)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 骨 / 骨粗鬆症 / 骨細胞 / エピゲノム / 骨形成

Research Abstract

MC3T3E1 cells treated with differentiation medium could not express osteocyte marker genes. Therefore, we focused on epigenetic regulation during osteocyte differentiation. ChIP analyses revealed that methylation levels of H3K4 and K27 on transcriptional start sites of osteocyte marker genes were bivalent status, suggesting that demethylation of H3K27 might to be essential for the differentiation from osteoblast to osteocyte. To examine physiological impact of this phenomenon, we generated flox mice of Kdm6A, demethylace for H3K27.

Research Products

• [Journal Article] Nuclear Receptors in Bone Physiology and Diseases (2013)
  • Author(s): Imai Y, Youn MY, Inoue K, Takada I, Kouzmenko A, Kato S
  • Journal Title: Physiol Rev Volume: 93(2) Pages: 481-523
  • Peer Reviewed
• [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control (2013)
  • Author(s): Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K,Sato T, Kawano H, Aihara K, Nakamichi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S,Imai Y.
  • Journal Title: Endocrinology Volume: 154(3) Pages: 1008-20
  • Peer Reviewed
• [Journal Article] Epigenetic Regulation of Adipogenesisby PHF2 Histone Demethylase (2013)
  • Author(s): Okuno Y, Ohtake F, Igarashi K, Kanno J, Matsumoto T, Takada I, Kato S, Imai Y.
  • Journal Title: Diabetes Volume: 62(5) Pages: 1426-34
  • Peer Reviewed
• [Journal Article] 【骨と多臓器ネットワーク】性ホルモンと骨 (2013)
  • Author(s): 今井祐記
  • Journal Title: Clinical Calcium Volume: 23巻2号 Pages: 211-217
• [Journal Article] 【性決定分化の制御システム:疾患性差・性転換をもたらす♂化・♀化のせめぎ合い】骨伸長と性差 (2013)
  • Author(s): 今井祐記
  • Journal Title: 細胞工学 Volume: 32巻2号 Pages: 199-202
• [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control (2013)
  • Author(s): Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Naka michi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y.
  • Journal Title: Endocrinology. Volume: 154 Issue: 3 Pages: 1008-20
  • DOI: 10.1210/en.2012-1542
  • Peer Reviewed
• [Journal Article] Epigenetic Regulation of Adipogenesis by PHF2 Histone Demethylase (2013)
  • Author(s): Okuno Y
  • Journal Title: Diabetes Volume: in press Issue: 5 Pages: 1426-34
  • DOI: 10.2337/db12-0628
  • Peer Reviewed
• [Journal Article] Nuclear Receptors in Bone Physiology and Diseases (2013)
  • Author(s): Imai Y
  • Journal Title: Physiol Rev. Volume: in press
  • Peer Reviewed
• [Journal Article] Female sex hormones ameliorate arthritis in SKG mice (2013)
  • Author(s): Inoue K
  • Journal Title: Biochem Biophys Res Commun. Volume: in press
  • Peer Reviewed
• [Journal Article] JMJD5, a JmjC-domain-containingprotein, negatively regulates osteoclastogenesis through facilitating NFATc1 protein degradation. (2012)
  • Author(s): Youn MY, Yokoyama A, Fujiyama- Nakamura S, Ohtake F, Minehata KI, Yasuda H, SuzukiT, Kato S, Imai Y.
  • Journal Title: J Biol Chem Volume: 87(16) Pages: 12994-3004
  • Peer Reviewed
• [Journal Article] 男性ホルモンの骨代謝における役割 (2012)
  • Author(s): 今井祐記
  • Journal Title: 内分泌・糖尿病・代謝内科 Volume: 34巻5号 Pages: 474-477
  • NAID: 40019350449
• [Journal Article] 破骨細胞分化におけるエピジェネティック制御 (2012)
  • Author(s): 延〓榮 加藤茂明 今井祐記
  • Journal Title: Clinical Calcium Volume: 22巻5号 Pages: 11-18
  • NAID: 130005008950
• [Journal Article] アンドロゲン受容体機能解明へのゲノムワイド解析 (2012)
  • Author(s): 今井祐記
  • Journal Title: Clinical Calcium Volume: 22巻5号 Pages: 37-42
• [Journal Article] エストロゲンと骨細胞 (2012)
  • Author(s): 金藤紫乃今井祐記
  • Journal Title: Clinical Calcium Volume: 22巻5号 Pages: 121-126
• [Journal Article] 骨吸収における正と負のエピゲノム制御 (2012)
  • Author(s): 今井祐記 延〓榮 加藤茂明
  • Journal Title: 炎症と免疫 Volume: 20巻3号 Pages: 16-21
• [Journal Article] ASBMR 2011 REPORT 基礎研究トピックス (2012)
  • Author(s): 今井祐記
  • Journal Title: Clinical Calcium Volume: 22巻1号 Pages: 108-110
• [Journal Article] JMJD5, a Jumonji C(JmjC) domain-containing protein, negatively regulates osteoclastogenesis by facilitating NFATc1 protein degradation (2012)
  • Author(s): Youn, M.-Y., Imai, Y., et al.
  • Journal Title: J Biol Chem Volume: 287 Issue: 16 Pages: 12994-13004
  • DOI: 10.1074/jbc.m111.323105
  • Peer Reviewed
• [Journal Article] JMJD5, a JmjC-domain-containing protein, negatively regulates osteoclastogenesis through facilitating NFATc1 protein degradation. (2012)
  • Author(s): Youn MY, Yokoyama A, Fujiyama-Nakamura S, Ohtake F, Minehata KI, Yasuda H, Suzuki T, Kato S, Imai Y.
  • Journal Title: J Biol Chem. Volume: Epub
  • Peer Reviewed
• [Journal Article] GlcNAcylation of histone H2B facilitates its monoubiquitination (2011)
  • Author(s): Fujiki R, Hashiba W, Sekine H, Yokoyama A, Chikanishi T, Ito S, Imai Y, Kim JH, He HH, Igarashi K,Kanno J, Ohtake F, Kitagawa H, Roeder R, Brown M, Kato S
  • Journal Title: Nature Volume: 480(7378) Pages: 557-60
  • Peer Reviewed
• [Journal Article] Local delivery of siRNA using a biodegradable polymer application to enhance BMP-induced bone formation (2011)
  • Author(s): Manaka T, Suzuki A, Takayama K, Imai Y, Nakamura H, Takaoka K.
  • Journal Title: Biomaterials Volume: 32(36) Pages: 9642-8
  • Peer Reviewed
• [Journal Article] Conditional deletion of Bmpr1a in differentiated osteoclasts increases osteoblastic bone formation, increasing volume of remodeling bone inmice (2011)
  • Author(s): Okamoto M, Murai J, Imai Y, Ikegami D, Kamiya N, Kato S, Mishina Y, Yoshikawa H, Tsumaki N
  • Journal Title: J Bone Miner Res Volume: 26(10) Pages: 2511-22
  • Peer Reviewed
• [Journal Article] Targeting Fas/FasL signaling, a new strategy for maintaining bone health (2011)
  • Author(s): Imai Y, Kouzmenko A, Kato S
  • Journal Title: Expert Opin Ther Targets Volume: 15(10) Pages: 1143-5
  • Peer Reviewed
• [Journal Article] Targeting Androgen Receptor in EstrogenReceptor-Negative Breast Cancer (2011)
  • Author(s): Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS, Brown M
  • Journal Title: Cancer Cell Volume: 20(1) Pages: 119-31
  • Peer Reviewed
• [Journal Article] Signal-sensing activation of a histone lysine demethylase complex (2011)
  • Author(s): Baba A, Ohtake F, Okuno Y, Yokota K, Okada M, Imai Y, Ni M, Meyer CA, Igarashi K, Kanno J, Brown M, Kato S
  • Journal Title: Nat Cell Biol Volume: 13(6) Pages: 669-76
  • Peer Reviewed
• [Journal Article] Erk kinases control plasma cell differentiation by regulating expression of Blimp-1 (2011)
  • Author(s): Yasuda T, Kometani K, Takahashi N, Imai Y, Aiba Y, Kurosaki T
  • Journal Title: Sci Signal Volume: 4(169) Pages: 25-25
  • Peer Reviewed
• [Journal Article] 骨組織・骨代謝と核内性ホルモン受容体の機能 (2011)
  • Author(s): 今井祐記,加藤茂明
  • Journal Title: 日本臨床 Volume: 69巻第7号 Pages: 1198-1202
• [Journal Article] 【性差科学の現状】女性ホルモン受容体による骨代謝制御の分子機構 (2011)
  • Author(s): 今井祐記,加藤茂明
  • Journal Title: ファルマシア Volume: 47巻3号 Pages: 203-207
• [Journal Article] GlcNAcylation of histone H2B facilitates its monoubiquitination (2011)
  • Author(s): Fujiki R, Hashiba W, Sekine H, Yokoyama A, Chikanishi T, Ito S, Imai Y, Kim J, He HH, Igarashi K, Kanno J, Ohtake F, Kitagawa H, Roeder RG, Brown M, Kato S
  • Journal Title: Nature Volume: 480(7378) Issue: 7378 Pages: 557-560
  • DOI: 10.1038/nature10656
  • Peer Reviewed
• [Journal Article] Local delivery of siRNA using a biodegradable polymer application to enhance BMP-induced bone formation. (2011)
  • Author(s): Manaka T, Suzuki A, Takayama K, Imai Y, Nakamura H, Takaoka K.
  • Journal Title: Biomaterials Volume: 32 Pages: 9642-8
  • Peer Reviewed
• [Journal Article] Conditional deletionof Bmpr1ab in differentiatedosteoclasts increases osteoblastic boneformation,increasing volume ofremodeling bone in mice. (2011)
  • Author(s): Okamoto,M.,Murai,J.,Imai,Y.,Ikegami,D.,Kamiya,N.,Kato,S.,Mishita,Y.,Yoshikawa,H.and Tsumaki,N
  • Journal Title: J.BoneMiner.Res. Volume: 26巻 Issue: 10 Pages: 2511-22
  • DOI: 10.1002/jbmr.477
  • Peer Reviewed
• [Journal Article] Targeting Androgen Receptor in Estrogen Receptor-Negative Breast Cancer (2011)
  • Author(s): Ni M, Chen Y, Bailey ST, Imai Y, Liu XS, Brown M
  • Journal Title: Cancer Cell Volume: 20 Pages: 119-31
  • Peer Reviewed
• [Journal Article] Signal-sensing activation of a histone lysine demethylase complex (2011)
  • Author(s): Baba A, Ohtake F, Okuno Y, Yokota K, Okada M, Imai Y, Ni M, Meyer CA, Igarashi K, Kanno J, Brown M, Kato S.
  • Journal Title: Nat Cell Biol Volume: 13 Pages: 669-76
  • Peer Reviewed
• [Journal Article] Erk kinases control plasma cell differentiation by regulating expression of Blimp-1 (2011)
  • Author(s): Yasuda T, Kometani K, Takahashi N, Imai Y, Aiba Y, Kurosaki T.
  • Journal Title: Sci Signal. Volume: 4
  • Peer Reviewed
• [Journal Article] Female sex hormones ameliorate arthritis in SKG mice
  • Author(s): Inoue K, Inoue E, Imai Y.
  • Journal Title: Biochem Biophys Res Commun
  • Peer Reviewed
• [Presentation] 骨代謝制御における性ホルモン受容体の生体内機能解明 (2012)
  • Author(s): 今井祐記
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-16
• [Presentation] Estrogen Exerts Osteoprotective Function through Facilitating Bone Formation via ERα in Osteocytes (2012)
  • Author(s): Yuuki Imai et al.
  • Organizer: 15th International Congress onHormonal Steroids and Hormones & Cancer
  • Place of Presentation: 金沢
  • Year and Date: 2012-11-16
• [Presentation] 軟骨代謝制御における性ホルモン受容体の機能解析 (2012)
  • Author(s): 今井祐記ら
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-10-26
• [Presentation] 破骨細胞分化におけるエピジェネティック制御 (2012)
  • Author(s): 今井祐記、延〓榮
  • Organizer: 第39回日本毒性学会学術年会
  • Place of Presentation: 仙台
  • Year and Date: 2012-07-17
• [Presentation] 性ホルモン受容体による骨代謝調節 (2012)
  • Author(s): 今井祐記
  • Organizer: 第54回日本老年医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-06-29
• [Presentation] 性ホルモン欠乏による骨粗鬆症の分子基盤 (2012)
  • Author(s): 今井祐記
  • Organizer: 第12回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-23
• [Presentation] Osteoblastic Androgen Receptor mediates androgenic anabolic actions in Bone remodeling今井祐記ら骨細胞における ERa の高次機能解析 (2012)
  • Author(s): Yuuki Imai et al.
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 東京
• [Presentation] Osteoblastic Androgen Receptor mediates androgenic anabolic actions in Bone remodeling (2012)
  • Author(s): Yuuki Imai
  • Organizer: Keystone Symposia
  • Place of Presentation: Whistler, British Columbia, Canada
• [Presentation] アンドロゲンによる骨同化作用の分子メカニズム解明 (2011)
  • Author(s): 今井祐記ら
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2011-07-28
• [Presentation] Identification of Androgen Receptor Function in Osteoblast by Genome-wide Approach Using ChIP-seq (2011)
  • Author(s): Yuuki Imai et al
  • Organizer: IBMS/ECTS
  • Place of Presentation: ギリシャ、アテネ
  • Year and Date: 2011-05-10
• [Presentation] アンドロゲンによる骨同化作用の分子メカニズム解明 (2011)
  • Author(s): 今井祐記ら
  • Organizer: 日本内分泌学会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-21
• [Presentation] Androgen Directly Exerts Anabolic Action through Osteoblastic Androgen Receptor (2011)
  • Author(s): Yuuki Imai et al
  • Organizer: ASBMR 2011
  • Place of Presentation: 米国、サンデ ィエゴ
• [Presentation] アンドロゲンによる骨同化作用の分子メカニズム解明 (2011)
  • Author(s): 今井祐記
  • Organizer: 第８４回日本内分泌学会
  • Place of Presentation: 神戸
• [Presentation] Identification of Androgen Receptor Function in Osteoblast by Genome-wide Approach Using ChIP-seq (2011)
  • Author(s): 今井祐記
  • Organizer: The 3rd Join Meeting of ECTS & IBMS
  • Place of Presentation: アテネ、ギリシャ
• [Presentation] アンドロゲンによる骨同化作用の分子メカニズム解明 (2011)
  • Author(s): 今井祐記
  • Organizer: 第29回日本骨代謝学会
  • Place of Presentation: 大阪
• [Presentation] Androgen Directly Exerts Anabolic Action through Osteoblastic Androgen Receptor (2011)
  • Author(s): 今井祐記
  • Organizer: ASBMR2011
  • Place of Presentation: サンディエゴ、USA
• [Presentation] 破骨細胞分化におけるエピジェネティック制御
  • Author(s): 今井祐記
  • Organizer: 第39回日本毒性学会学術年会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] 骨細胞におけるERαの高次機能解析
  • Author(s): 今井祐記
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Osteoblastic Androgen Receptor mediates androgenic anabolic actions in Bone remodeling
  • Author(s): Yuuki Imai
  • Organizer: 第30回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 軟骨代謝制御における性ホルモン受容体の機能解析
  • Author(s): 今井祐記
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] Estrogen Exerts Osteoprotective Function through Facilitating Bone Formation via ERα in Osteocytes
  • Author(s): Yuuki Imai
  • Organizer: 15th International Congress on Hormonal Steroids and Hormones & Cancer
  • Place of Presentation: 金沢
  • Invited
• [Book] バイオ実験に絶対使える統計の基本Q&A (2012)
  • Author(s): 秋山徹、編集:井元清哉、河府和義、藤渕航
  • Publisher: 羊土社