The analysis of the cell death control by CDK6

• Project/Area Number: 18591654
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: HARA Nobuhiro The University of Tokyo, 医学部・附属病院, 助教 (00422296)
• Co-Investigator(Kenkyū-buntansha): FUKAI Atsushi 東京大学, 医学部・附属病院, 助教 (20422298) ; KAWANO Hirotaka 東京大学, 医学部・附属病院, 講師 (20345218) ; OGASAWARA Toru 東京大学, 医学部・附属病院, 講師 (20359623)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,040,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥540,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2007: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: CDK6 / Cyclin D1 / p53 / 軟骨細胞 / 骨芽細胞 / アポトーシス / Cyclin Dl

Research Abstract

骨・軟骨細胞の分化、増殖を調整する細胞周期関連分子CDK6に注目し、軟骨細胞及び骨芽細胞に特異的にCDK6を強制発現させる遺伝子改変マウスを作成し解析した。CDK6とCyclin D1を同時に発現させると、細胞増殖が促進されると同時に、癌抑制遺伝子であるp53依存的にアポトーシスが誘導されることを発見した。更に骨芽細胞でCDK6が誘導したアポトーシスは、Bcl-2の導入で救済され、骨量が著名に増加した。骨増殖症のモデルマウスになる可能性が示唆された。

Research Products

• [Journal Article] C/EBPβ promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57Kip2 (2009)
  • Author(s): Hirata M, Kugimiya F, Ohba S, Kawamura N, Ogasawara T, Kawasaki Y, Fukai A, Ikeda T, Nakamura K, Chung UI, and Kawaguchi H.
  • Journal Title: PLoS ONE 4(2) Pages: 4543-4543
  • Peer Reviewed
• [Journal Article] Aptitude of Auricular and Nasoseptal Chondrocytes Cultured under a Monolayer or Three-Dimensional Condition for Cartilage Tissue Engineering (2009)
  • Author(s): Asawa, Y., Ogasawara, T., Takahashi, T., Yamaoka, H., Nishizawa, S., Matsudaira, K., Mori, Y., Takato, T. and Hoshi, K.
  • Journal Title: Tissue Eng Part A Pages: 1109-18
  • Peer Reviewed
• [Journal Article] C/EBPβ Promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57Kip2. (2009)
  • Author(s): Makoto Hirata et al.
  • Journal Title: PLoS ONE 4
  • Peer Reviewed
• [Journal Article] Effects of transforming growth factor (TGF)-β1 in combination with fibroblast growth factor (FGF)-2 and insulin-like growth factor (IGF)-I on chondrocytes proliferation culture for the cartilage regenerative medicine. (2009)
  • Author(s): Toru Ogasawara et al.
  • Journal Title: Asian J Oral Maxillofac Surg (in press)
  • Peer Reviewed
• [Journal Article] Aptitude of Auricular and Nasoseptal Chondrocytes Cultured under a Monolayer or Three-Dimensional Condition for Cartilage Tissue Engineering (2009)
  • Author(s): Yukiyo Asawa et al.
  • Journal Title: Tissue Eng Part A (in press)
  • Peer Reviewed
• [Journal Article] Selection of highly osteogenic and chondrogenic cells from bone marrow stromal cells in biocompatible polymer-coated plate. (2009)
  • Author(s): Liu G et al.
  • Journal Title: J Biomed Mater Res A (in press)
  • Peer Reviewed
• [Journal Article] Growth factor contents of autologous human sera prepared by different production methods and their biological effects on chondrocytes (2008)
  • Author(s): Tanaka, Y., Ogasawara, T., Asawa, Y., Yamaoka, H., Nishizawa, S., Mori, Y., Takato, T. and Hoshi, K.
  • Journal Title: Cell Biol Int 32 Pages: 505-514
  • Peer Reviewed
• [Journal Article] Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity (2008)
  • Author(s): Ohba, S., Kawaguchi, H., Kugimiya, F., Ogasawara, T., Kawamura, N., Saito, T., Ikeda, T., Fujii, K., Miyajima, T., Kuramochi, A., Miyashita, T., Oda, H., Nakamura, K., Takato, T. and Chung, U.I.
  • Journal Title: Dev Cell 14 Pages: 689-699
  • Peer Reviewed
• [Journal Article] Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes (2008)
  • Author(s): Kawasaki, Y., Kugimiya, F., Chikuda, H., Kamekura, S., Ikeda, T., Kawamura, N., Saito, T., Shinoda, Y., Higashikawa, A., Yano, F., Ogasawara, T., Ogata, N., Hoshi, K., Hofmann, F., Woodgett, J.R., Nakamura, K., Chung, U.I. and Kawaguchi, H.
  • Journal Title: J Clin Invest 118 Pages: 2506-15
  • Peer Reviewed
• [Journal Article] Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity. (2008)
  • Author(s): Shinsuke Ohba et al.
  • Journal Title: Dev Cell 14 Pages: 689-699
  • Peer Reviewed
• [Journal Article] Phosphorylation of GSK-3β by cGMP-dependent protein kinase II Promotes hypertrophic differentiation of murine chondrocytes. (2008)
  • Author(s): Yosuke Kawasaki et al.
  • Journal Title: J Clin Invest 118 Pages: 2506-2515
  • Peer Reviewed
• [Journal Article] Growth factor contents of autologous human sera prepared by different production methods and their biological effects on chondrocytes. (2008)
  • Author(s): Yoko Tanaka et al.
  • Journal Title: Cell Biol Int 32 Pages: 505-514
  • Peer Reviewed
• [Journal Article] Growth Factor Contents of Autologous Human Sera Prepared by Different Production Methods and Their Biological Effects on Chondrocytes. (2008)
  • Author(s): Yoko Tanaka, et. al.
  • Journal Title: Cell Biology International (掲載確定)
  • Peer Reviewed
• [Journal Article] Three-dimensional microenvironments retain chondrocyte phenotypes during proliferation culture (2007)
  • Author(s): Takahashi T., Ogasawara T., Asawa Y., Mori Y., Uchinuma E., Takato T. and Hoshi K.
  • Journal Title: Tissue Engineering 13 Pages: 1583-1592
  • Peer Reviewed
• [Journal Article] Optimal combination of soluble factors for tissue engineering of permanent cartilage from cultured human chondrocytes (2007)
  • Author(s): Liu G., Kawaguchi H., Ogasawara T., Asawa Y., Kishimoto J.I., Takahashi T., Chung U.I., Yamaoka H., Asato H., Nakamura K., Takato T. and Hoshi K.
  • Journal Title: J Biol Chem 282 Pages: 20407-20415
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 Activity is essential for the Osseointegration of Dental Implants (2007)
  • Author(s): Chikazu D., Tomizuka K., Ogasawara T., Saijo H., Koizumi T., Mori Y., Yonehara Y., Susami T. and Takato T.
  • Journal Title: Int J Oral Maxillofac Surg 36 Pages: 441-446
  • Peer Reviewed
• [Journal Article] Optimal combination of soluble factors for tissue engineering of permanent cartilage from cultured human chondrocytes. (2007)
  • Author(s): Guangyao Liu, et. al.
  • Journal Title: J Biol Chem 282 Pages: 20407-20415
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 Activity is essential for the Osseointegration of Dental Implants. (2007)
  • Author(s): Daichi Chikazu, et. al.
  • Journal Title: Int. J. Oral. Maxillofac. Surg. 36 Pages: 441-446
  • Peer Reviewed
• [Journal Article] Three-Dimensional Microenvironments Retain Chondrocyte Phenotypes During Proliferation Culture (2007)
  • Author(s): Tsuguharu Takahashi, et. al.
  • Journal Title: Tissue Engineering 13 Pages: 1583-1592
  • Peer Reviewed
• [Journal Article] Carminerin contributes to chondrocyte calcification during endochondral ossification. (2006)
  • Author(s): Takashi Yamada, et al.
  • Journal Title: Nat Med l2 Pages: 665-670
• [Journal Article] Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials. (2006)
  • Author(s): Hisayo Yamaoka, et al.
  • Journal Title: J Biomed Mater Res A.78 Pages: 1-11
• [Journal Article] Suppression of adjuvant-induced arthritic bone destruct ion by cyclooxygenase-2 selective agents with and WithoUt inhibitory potency against carbonic anhydrase II. (2006)
  • Author(s): Mika Katagiri, et al.
  • Journal Title: J Bone Miner Res 21 Pages: 219-227
• [Journal Article] Selection of highly osteogenic and chondrogenic cells from bone marrow stromal cells in biocompatible polymer-coated plates
  • Author(s): Liu G., Iwata K., Ogasawara T,, Watanabe J., Fukazawa K., Ishihara K., Asawa Y., Fujihara Y., Chung U.I., Moro T., Takatori Y., Takato T. Nakamura K., Kawaguchi H., and Hoshi K.
  • Journal Title: J Biomed Mater Res A (in press)
  • Peer Reviewed
• [Journal Article] Effects of transforming growth factor (TGF)-β1 in combination with fibroblast growth factor (FGF)-2 and insulin-like growth factor (IGF)-I on chondrocytes proliferation culture for the cartilage regenerative medicine
  • Author(s): Ogasawara T,, Ohba S., Fujihara Y., Takahashi T., Liu G., Chikazu D., Suenaga H., Chung U.I., Yoda T., Mori Y., Susami T., Takato T., and Hoshi K.
  • Journal Title: Asian J Oral Maxillofac Surg (in press)
• [Presentation] 間葉系細胞の分化多能性維持機構におけるNanogの役割 (2009)
  • Author(s): 小笠原徹ほか
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪府大阪市
• [Presentation] 間葉系細胞の分化多能性維持機構におけるNanog の役割 (2008)
  • Author(s): 小笠原徹, 川口浩, 高戸毅, 星和人
  • Organizer: 第26回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場大阪
• [Presentation] C/EBPβ/p57K1P2 signaling maintains transition from proliferation to hypertrophic differentiation of chondrocytes during skeletal growth. (2008)
  • Author(s): Makoto Hirata et al.
  • Organizer: 30th Annual Meeting of the American Society for Bone and Mineral Research.
  • Place of Presentation: Montreal, Quebec, Canada
• [Presentation] C/EBP-beta promotes hypertrophic differentiation of chondrocytes through transactivation of p57Kip2 during endochondral ossification. (2008)
  • Author(s): Fumitaka Kugimiya et al.
  • Organizer: 2008 World Congress on Osteoarthritis
  • Place of Presentation: Rome, Italy
• [Presentation] 細胞周期分子による骨再生医療のための基礎的検討 (2007)
  • Author(s): 小笠原 徹, ほか
  • Organizer: 第6回 日本再生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-03-13
• [Presentation] 細胞周期分子による骨再生医療のための基礎的検討 (2007)
  • Author(s): 小笠原徹, 川口浩, 岡山博人, 高戸毅, 星和人
  • Organizer: 第6回日本再生医療学会総会
  • Place of Presentation: 横浜
• [Presentation] ヒト軟骨細胞の継代培養に伴う表面抗原の変化とその生物学的意義 (2007)
  • Author(s): 浅輪幸世, 小笠原徹, 高戸毅, 星和人
  • Organizer: 第6回日本再生医療学会総会
  • Place of Presentation: 横浜
• [Presentation] 軟骨細胞脱分化現象におけるFGF ファミリーの役割 (2007)
  • Author(s): 西澤悟, 山岡尚世, 小笠原徹, 浅輪幸世, 山岡桂子, 高戸毅, 星和人
  • Organizer: 第6回日本再生医療学会総会
  • Place of Presentation: 横浜
• [Presentation] Application of cell cycle factors to bone regeneration (2007)
  • Author(s): Ogasawara T., Hoshi K., Kawaguchi H., Ohba S., Chikazu D., Fujihara Y., Suenaga H., Mori Y., Susami T., Okayama H., Takato T.
  • Organizer: Tissue Engineering International & Regenerative Medicine Society Asia-Pacific Chapter Meeting 2007
  • Place of Presentation: Tokyo, Japan
• [Presentation] Changes in surface epitopes of human chondrocytes during a long-term culture and their biological significances (2007)
  • Author(s): Asawa Y., Ogasawara T., Takato T., Hoshi K.
  • Organizer: Tissue Engineering International & Regenerative Medicine Society Asia-Pacific Chapter Meeting 2007
  • Place of Presentation: Tokyo, Japan
• [Presentation] Cytological roles of the FGF family in the chondrocyte redifferentiation (2007)
  • Author(s): Nishizawa S., Yamaoka H., Ogasawara T., Asawa Y., Yamaoka K., Takato T., Hoshi K.
  • Organizer: Tissue Engineering International & Regenerative Medicine Society Asia-Pacific Chapter Meeting 2007
  • Place of Presentation: Tokyo, Japan
• [Presentation] Application of Cell Cycle Factors to Bone Regeneration. (2007)
  • Author(s): Toru Ogasawara, et. al.
  • Organizer: TERMIS-AP 2007
  • Place of Presentation: Tokyo
• [Presentation] 自家軟骨細胞から大量永久軟骨再生のための最適シグナル条件の系統的・網羅的検索 (2006)
  • Author(s): 星和人, 劉光耀, 小笠原徹, 浅輪幸世, 高橋嗣明, 鄭雄一, 高戸毅, 中村耕三, 川口浩
  • Organizer: 第24回日本骨代謝学会学術集会
  • Place of Presentation: 東京
• [Presentation] ptimal combination of soluble factors for Tissue Engineering of permanent cartilage with high quality and quantity from autologous human chondrocytes (2006)
  • Author(s): Hoshi K, Liu G, Ogasawara T, Asawa Y, Takahashi T, Yamaoka H, Chung U, Takato T, Nakamura K, Kawaguchi H.
  • Organizer: Twenty-Eighth Annual Meeting of the American Society for Bone and Mineral Research September
  • Place of Presentation: Pennsylvania Convention Center Philadelphia, Pennsylvania, USA