Development and medical application of peptide and RNA aptamers that bind to CCN2

2011 Fiscal Year Final Research Report

• Project/Area Number: 21592360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Okayama University
• Principal Investigator: KUBOTA Satoshi 岡山大学, 大学院・医歯薬学総合研究科, 准教授 (90221936)
• Co-Investigator(Kenkyū-buntansha): TAKIGAWA Masaharu 岡山大学, 大学院・医歯薬学総合研究科, 教授 (20112063) ; HATTORI Takako 岡山大学, 大学院・医歯薬学総合研究科, 助教 (00228488) ; NISHIDA Takashi 岡山大学, 大学院・医歯薬学総合研究科, 助教 (30322233) ; AOYAMA Eriko 岡山大学, 大学院・医歯薬学総合研究科, 助教 (10432650)
• Project Period (FY): 2009 – 2011
• Keywords: 口腔生化学 / 細胞生物学 / 再生医工学

Research Abstract

CCN2 is known to promote harmonized regeneration of bone and cartilage tissues and to be involved in fibrotic disorders of a variety of organs. Therefore, regulating CCN2 function is of great significance in the field of regenerative medicine and fibrosis therapeutics. In this study, we designed, synthesized and evaluated the effect of aptamers that bind to CCN2, in order to control the molecular action of CCN2. As a result, we could obtain a few aptamers that could promote cartilage regeneration, or might regulate bone remodeling.

Research Products

• [Journal Article] Role of low-density lipoprotein receptor related protein 1(LRP1) in CCN2/connective tissue growth factor(CTGF) protein transport in chondrocytes. (2012)
  • Author(s): Kawata., K., S. Kubota, T. Eguchi, E. Aoyama, N. Moritani, S. Kondo, T. Nishida and M. Takigawa
  • Journal Title: J Cell Sci. Volume: (in press)
  • Peer Reviewed
• [Journal Article] CCN2 and orofacial tissue development and remodeling. (2012)
  • Author(s): Kubota, S.
  • Journal Title: Jpn. Dental Sci.
  • Peer Reviewed
• [Journal Article] The role of CCN2 in cartilage and bone development (2011)
  • Author(s): Kubota, S., and M. Takigawa.
  • Journal Title: J. Cell Commun. Signal. Volume: 5 Pages: 209-217
  • Peer Reviewed
• [Journal Article] Differential roles of CCN family proteins during osteoblast differentiation : involvement of Smad and MAPK signaling pathways (2011)
  • Author(s): EKawaki, H., S. Kubota, A. Suzuki, M. Suzuki, K. Kohsaka, K. Hoshi, T. Fujii, N. Lazar, T. Ohgawara, T. Maeda, B. Perbal, T. Takano-Yamamoto and M. Takigawa.
  • Journal Title: Bone Volume: 49 Pages: 975-989
  • Peer Reviewed
• [Journal Article] Effect of CCN2 on FGF2-Induced Proliferation and MMP9 and MMP13 Productions by Chondrocytes (2011)
  • Author(s): Nishida, T., S. Kubota, E. Aoyama, D. Janune, A. Maeda and M. Takigawa
  • Journal Title: Endocrinology Volume: 152 Pages: 4232-4241
  • Peer Reviewed
• [Journal Article] Binding of glyceraldehyde-3-phosphate dehydrogenase to the cis-acting element of structure-anchored repression in ccn2 mRNA. (2011)
  • Author(s): Kondo, S., S. Kubota, Y. Mukudai, T. Nishida, Y. Yoshihama, T. Shirota, S. Shintani and M. Takigawa
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 405 Pages: 382-387
  • Peer Reviewed
• [Journal Article] CCN family 2/connective tissue growth factor(CCN2/CTGF) promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein(DC-STAMP) (2011)
  • Author(s): Nishida, T., K. Emura, S. Kubota, K. M. Lyons and M. Takigawa
  • Journal Title: J Bone Miner Res. Volume: 26 Pages: 351-363
  • Peer Reviewed
• [Journal Article] Mechanical stretch increases CCN2/CTGF expression in anterior cruciate ligament-derived cells. (2011)
  • Author(s): Miyake, Y., T. Furumatsu, S. Kubota, K. Kawata, T. Ozaki and M. Takigawa.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 409 Pages: 247-252
  • Peer Reviewed
• [Journal Article] Increases in p53 expression induce CTGF synthesis by mouse and human hepatocytes and result in liver fibrosis in mice (2011)
  • Author(s): Kodama, T., S. Kubota(14番目), M. Takigawa(15番目: 18名略)
  • Journal Title: J Clin Invest Volume: 121 Pages: 3343-3356
  • Peer Reviewed
• [Journal Article] Association of the metastatic phenotype with CCN family members among breast and oral cancer cells (2011)
  • Author(s): Ohgawara, T., S. Kubota, H. Kawaki, N. Kurio, T. Abd El Kader, M, Hoshijima, D. Janune, T. Shimo, B. Perbal, A. Sasaki and M. Takigawa
  • Journal Title: J. Cell Commun. Signal Volume: 5 Pages: 291-299
  • Peer Reviewed
• [Journal Article] Identification of miR-1 as a micro RNA that supports late-stage differentiation of growth cartilage cells (2010)
  • Author(s): Sumiyoshi, K., S. Kubota, T. Ohgawara, K. Kawata, T. Nishida, T. Shimo, T. Yamashiro and M. Takigawa.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 402 Pages: 286-290
  • Peer Reviewed
• [Journal Article] Nicotine-induced CCN2 : from smoking to periodontal fibrosis. (2010)
  • Author(s): Takeuchi, K., S. Kubota, E. Murakashi, Y. Zhou, K. Endo, P. S. Ng, M. Takigawa, and Y. Numabe.
  • Journal Title: J. Dent. Res. Volume: 89 Pages: 34-39
  • Peer Reviewed
• [Journal Article] Thrombopoietic-mesenchymal interaction that may facilitate both endochondral ossification and platelet maturation via CCN2 (2010)
  • Author(s): Sumiyoshi, K., S. Kubota, R. A. Furuta, K. Yasui, E. Aoyama, H. Kawaki, K. Kawata, T. Ohgawara, T. Yamashiro, and M. Takigawa
  • Journal Title: J Cell Commun Signal. Volume: 4 Pages: 5-14
  • Peer Reviewed
• [Journal Article] Design and utility of CCN2 anchor peptide aptamers (2010)
  • Author(s): Kawaki H, S. Kubota, E. Aoyama, N. Fujita, H. Hanagata, A. Miyauchi, K. Nakai and M. Takigawa
  • Journal Title: Biochimie Volume: 92 Pages: 1010-1015
  • Peer Reviewed
• [Journal Article] N-terminal domains of CCN protein 2/connective tissue growth factor bind to aggrecan. (2009)
  • Author(s): Aoyama E., T. Hattori, M. Hoshijima, D. Araki, T. Nishida, S. Kubota, and M. Takigawa
  • Journal Title: Biochem. J. Volume: 420 Pages: 413-420
  • Peer Reviewed
• [Journal Article] Effect of TGF-β1 on CCN2/CTGF in normal human gingival fibroblasts and periodontal ligament cells (2009)
  • Author(s): Takeuchi, H., S. Kubota, E. Murakashi, T. Fukada, S. Hashimoto, M. Takigawa and Y. Numabe
  • Journal Title: J. Perio. Res. Volume: 44 Pages: 161-169
  • Peer Reviewed
• [Presentation] CCN2 promotes osteoclastogenesis via induction of and interaction with DC-STAMP and by enhancing RANKL signaling via interaction with RANK and osteoprotegerin (2011)
  • Author(s): Nishida, T.
  • Organizer: Cell Signaling Networks 2011 : the 13th IUBMB Conference, the 1st PABMB Conference and the 3rd Meetings of the Signal Transduction Branch & Oxidative Stress Branches of SMB
  • Place of Presentation: Merida、Mexico
  • Year and Date: 20111022-27
• [Presentation] Role of CCN2 in the remodeling of periodontal tissue upon nicotine exposure. Novel targets for cancer and connective tissue diseases (2011)
  • Author(s): Kubota, S.
  • Organizer: A meeting sponsored by the International CCN Society
  • Place of Presentation: Vancouver、Canada
  • Year and Date: 20110924-27
• [Presentation] RANK結合タンパク質CCN2/CTGFはRANK-RANKLシグナルを促進する (2011)
  • Author(s): 青山絵理子
  • Organizer: 第29回骨代謝学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 20110728-30
• [Presentation] The role of CCN2/CTGF binding to receptor activator of NF-κB(RANK) in the RANK-RANK ligand system (2010)
  • Author(s): Aoyama, E.
  • Organizer: BMB2010(第83回日本生化学会大会、第33回日本分子生物学会年会)
  • Place of Presentation: 神戸市
  • Year and Date: 20101207-10
• [Presentation] CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling (2010)
  • Author(s): Aoyama, E
  • Organizer: Sixth International Workshop on the CCN Family of Genes
  • Place of Presentation: Newcastle、Northern Ireland
  • Year and Date: 20101020-24
• [Presentation] Screening of CCN2-binding peptides and its scientific utility (2010)
  • Author(s): Kubota, S.
  • Organizer: Sixth International Workshop on the CCN Family of Genes
  • Place of Presentation: Newcastle、Northern Ireland
  • Year and Date: 20101020-24
• [Presentation] CCN family 2/connective tissue growth factor(CCN2/CTGF) promotes osteoclastogenesis via interaction with dendritic cell-specific transmembrane protein(DC-STAMP) (2009)
  • Author(s): Nishida, T
  • Organizer: The 31st Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Denver、USA
  • Year and Date: 20090911-15
• [Presentation] CCNファミリー遺伝子の転写後制御とその生物学的意義 (2009)
  • Author(s): 久保田聡
  • Organizer: 第3回日本CCNファミリー研究会シンポジウム
  • Place of Presentation: 岡山市
  • Year and Date: 20090828-29
• [Presentation] CCN family proteins and micro RNAs : Extracellular and intracellular conductors of molecular networks (2009)
  • Author(s): Kubota, S.
  • Organizer: The Second International Symposium of Medical and Dental Education in Okayama
  • Place of Presentation: 岡山市
  • Year and Date: 20090517-18
• [Presentation] 遺伝子発現の転写後調節の重要性:組織再生因子CCN2の場合 (2009)
  • Author(s): 久保田聡
  • Organizer: 岡山大学大学院医歯薬学総合研究科機能再生・再建科学専攻主催ミニシンポジウム
  • Place of Presentation: 岡山市
  • Year and Date: 2009-08-11
• [Book] In : Encyclopedia of Signaling Molecules(Sangdun Choi ed) (2012)
  • Author(s): Kubota, S. and M. Takigawa
  • Publisher: Springer
• [Book] Nucleophosmin/B23 : A multifunctional regulator that determines the fate of ccn2 mRNA. In : CCN Proteins in Health and Disease(A. Perbal, M. Takigawa & B. Perbal eds) (2010)
  • Author(s): Kubota, S., Y. Mukudai, H. Kawaki, S. Kondo, T. Eguchi, K. Sumiyoshi, T. Ohgawara, T. Shimo and M. Takigawa
  • Total Pages: 41-55
  • Publisher: Springer
• [Book] Novel transcriptional regulation of CCN2/CTGF by nuclear translocation of MMP3. In : CCN Proteins in Health and Disease(A. Perbal, M. Takigawa & B. Perbal eds) (2010)
  • Author(s): Eguchi, T., S. Kubota, K. Kawata, Y. Mukudai, J. Uehara, T. Ohgawara, S. Ibaragi, A. Sasaki, T. Kuboki and M. Takigawa
  • Total Pages: 255-264
  • Publisher: Springer
• [Book] Cooperative regulation of cell proliferation and differentiation by CCN2 and CCN3. In : CCN Proteins in Health and Disease(A. Perbal, M. Takigawa & B. Perbal eds) (2010)
  • Author(s): Takigawa, M., H. Kawaki, S. Kubota, K. M. Lyons and B. Perbal
  • Total Pages: 105-109
  • Publisher: Springer