Regulation of CCN family gene expression via micro RNA regulatory network and its Biological signficance

2008 Fiscal Year Final Research Report

• Project/Area Number: 19592142
• 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 Okayama University, 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)
• Project Period (FY): 2007 – 2008
• Keywords: 口腔生化学 / ゲノム医化学 / 細胞医化学

Research Abstract

マイクロRNA(miRNA)は小分子noncoding RNA(ncRNA)であり、個々のmiRNAが数千のmRNAの3'非翻訳領域を標的として、遺伝子の発現をネットワーク的に制御する。本研究ではCCNファミリー遺伝子の代表的メンバーであり、間葉系組織の成長ならびに再生を指揮するCCN2遺伝子が特定のmiRNAの制御ネットワーク下にあることを実証した。さらに、このmiRNAによる制御が、軟骨細胞の成熟形質の獲得・維持に重要であることも明らかとなった。またmiRNAの作用機構や軟骨細胞後期分化における役割を今後解明していく上で、有用な知見をも得ることができた。

Research Products

• [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. (in press)
  • Peer Reviewed
• [Journal Article] Regulation of chondrocytic phenotype by micro RNA 18a : Involvement of Ccn2/Ctgf as a major target gene (2009)
  • Author(s): Ohgawara, T., S.Kubota, H.Kawaki, S.Kondo, T.Eguchi, N.Kurio, E.Aoyama, A.Sasaki, and M.Takigawa
  • Journal Title: FEBS Lett 583 Pages: 1006-1010
  • 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 44 Pages: 161-169
  • Peer Reviewed
• [Journal Article] CCN family 2/connective tissue growth factor (CCN2/CTGF) regulates the expression of Vegf through Hif-1 α expression in a chondrocytic cell line, HCS-2/8 (2009)
  • Author(s): Nishida, T.S.Kondo, A.Maeda, S.Kubota, K.M.Lyons, and M.Takigawa
  • Journal Title: under hypoxic condition(Bone) 44 Pages: 24-31
  • Peer Reviewed
• [Journal Article] CCN family 2/connective tissue growth factor modulates BMP signalling as a signal conductor, which action regulates the proliferation and differentiation of chondrocytes (2009)
  • Author(s): Maeda A, T.Nishida, E.Aoyama, S.Kubota, K.M.Lyons, T.Kuboki, and M.Takigawa
  • Journal Title: J Biochem 145 Pages: 207-216
  • Peer Reviewed
• [Journal Article] Post-transcriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation (2008)
  • Author(s): Mukudai, Y., S.Kubota, H.Kawaki, S.Kondo, T.Eguchi, K.Sumiyoshi, T.Ohgawara, T.Shimo, and M.Takigawa
  • Journal Title: Mol. Cel 1. Biol. 28 Pages: 6134-6147
  • Peer Reviewed
• [Journal Article] Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 revealed by a comprehensive analysis of the CCN family proteins in cartilage (2008)
  • Author(s): Kawaki, T., S.Kubota, A.Suzuki, N.Lazar, T.Yamada, T.Matsumura, T.Ohgawara, T.Maeda, B.Perbal, K.M.Lyons, and M.Takigawa
  • Journal Title: J. Bone Miner. Res 23 Pages: 1751-1764
  • Peer Reviewed
• [Journal Article] Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel (2008)
  • Author(s): Kikuchi, T., S.Kubota, K.Asaumi, H.Kawaki, K.Nishida, T., Kawata, S.Mitani, Y.Tabata, T.Ozaki, and M.Takigawa
  • Journal Title: Tissue Engineering Part A 14 Pages: 1089-1098
  • Peer Reviewed
• [Journal Article] Role of Mechanical-stress inducible protein Hcs24/CTGF/CCN2 in cartilage growth and regeneration (2008)
  • Author(s): Nishida, T., A.Maeda, S.Kubota and M.Takigawa
  • Journal Title: -Mechanical stress induces expression of Hcs24/CTGF/CCN2 in a human chondrocytic cell line HCS-2/8, rabbit hyaline costal chondrocytes and meniscus tissue cells-(Biorheology) 45 Pages: 289-299
  • Peer Reviewed
• [Journal Article] Novel transcription factor-like function of human MMP3 regulating CTGF/CCN2 gene (2008)
  • Author(s): Eguchi, T., S.Kubota, K.Kawata, Y.Mukudai, J.Uehara, T.Ohgawara, S.Ibaragi, S.Sasaki, T.Kuboki and M.Takigawa
  • Journal Title: Mol. Cell. Biol. 28 Pages: 2391-2413
  • Peer Reviewed
• [Journal Article] Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2 (2008)
  • Author(s): Ono, M., S.Kubota, T.Fujisawa, W.Sonoyama, H.Kawaki, K.Akiyama, M.Oshima, T.Nishida, Y.Yoshida, K.Suzuki, M.Takigawa and T.Kuboki
  • Journal Title: Cell Transplant 17 Pages: 231-240
  • Peer Reviewed
• [Journal Article] Functional requirement of CCN2 for intramembranous bone formation in embryonic mice (2008)
  • Author(s): Kawaki, H., S.Kubota, A.Suzuki, T.Yamada, T.Matsumura, T.Mandai, M.Yao, T.Maeda, K.M.Lyons and M.Takigawa
  • Journal Title: Biochem. Biophys. Res. Commun 366 Pages: 450-456
  • Peer Reviewed
• [Journal Article] Clinical significance and function of connective tissue growth factor (CTGF/CCN2) in osteolytic mandible squamous cell carcinoma (2008)
  • Author(s): Shimo, T., S.Kubota, T.Goda, Y.Yoshihama, N.Kurio, T.Nishida, M.Takigawa and A.Sasaki
  • Journal Title: Anticancer Res. 28 Pages: 2343-2348
  • Peer Reviewed
• [Journal Article] CCN family 2 / Connective tissue growth factor (CCN2/CTGF) stimulates proliferation and differentiation of auricular chondrocytes (2008)
  • Author(s): Fujisawa T, T.Hattori, M.Ono, J.Uehara, S.Kubota, T.Kuboki and M.Takigawa
  • Journal Title: Osteoarthritis Cartilage 16 Pages: 787-795
  • Peer Reviewed
• [Journal Article] Plasma connective tissue growth factor is a novel potential biomarker of cardiac dysfunction in patients with chronic heart failure (2008)
  • Author(s): Koitabashi, N., M.Arai, K.Niwano, A.Watanabe, M.Endoh, M.Suguta, T.Yokoyama, H.Tada, T.Toyama, H.Adachi, S.Naito, S.Oshima, T.Nishida, S.Kubota, M.Takigawa and M.Kurabayashi
  • Journal Title: Eur. J. Heart Failure 10 Pages: 373-379
  • Peer Reviewed
• [Journal Article] Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes (2007)
  • Author(s): Yanagita, T., S.Kubota, K.Kawata, H.Kawaki, S.Kondo, T.Takano-Yamamoto, S.Tanaka and M.Takigawa
  • Journal Title: FEBS J. 274 Pages: 1655-1665
  • Peer Reviewed
• [Journal Article] Promotion of attachment of human bone marrow stromal cells by CCN2. Biochem (2007)
  • Author(s): Ono, M., S.Kubota, T.Fujisawa, W.Sonoyama, H.Kawaki, K.Akiyama, M.Oshima, T.Nishida, Y.Yoshida, K.Suzuki, M.Takigawa and T.Kuboki
  • Journal Title: Biophys. Res. Commun 357 Pages: 20-25
  • Peer Reviewed
• [Journal Article] Different transcriptional strategies of ccn2/ctgf gene induction between human chondrocytic and breast cancer cell lines (2007)
  • Author(s): Eguchi, T., S.Kubota, K.Kawata, Y.Mukudai, T.Ohgawara, K.Miyazono K.Nakao, S.Kondo and M.Takigawa
  • Journal Title: Biochimie 89 Pages: 278-288
  • Peer Reviewed
• [Journal Article] Gene expression and distribution of connective tissue growth factor (CCN2/CTGF) during secondary ossification center formation (2007)
  • Author(s): Oka, M., S.Kubota, S.Kondo, T.Eguchi, C.Kuroda, K.Kawata, S.Minagi and M.Takigawa
  • Journal Title: J. Histochem. Cytochem 55 Pages: 1245-1255
  • Peer Reviewed
• [Journal Article] Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis (2007)
  • Author(s): Koitabashi, N., M.Arai, S.Kogure, K.Niwano, A.Watanabe, Y.Aoki, T.Maeno, T.Nishida, S.Kubota, M.Takigawa and M.Kurabayashi
  • Journal Title: Hypertension 49 Pages: 1120-1127
  • Peer Reviewed
• [Presentation] Micro RNA 18 regulates chondrocytic phenotype : Involvement of Ccn/Ctgf as a major target gene (2009)
  • Author(s): Ohgawara, T., S.Kubota, H.Kawaki, S.Kondo, T.Eguchi, A.Sasaki and M.Takigawa
  • Organizer: 2nd Joint Meeting, International Bone & Mineral Society and Australian and New Zealand Bone & Mineral Society
  • Place of Presentation: Sydney, Australia
  • Year and Date: 20090300
• [Presentation] Expression and mechanisms of connective tissue growth factor (CCN2/CTGF) induction in osteolytic jaw invasion of human oral squamous cell carcinoma (2009)
  • Author(s): Shimo, T., S.Kubota, T.Goda, Y.Yoshihama, N.Kurio, T.Okui, D.Yamamoto, A.Ono, M.Takigawa and A.Sasaki
  • Organizer: ORS 55th Annual Meeting
  • Place of Presentation: Las Vegas, U.S.A.
  • Year and Date: 20090200
• [Presentation] Novel transcriptional regulation of CCN2/CTGF by nuclear translocated MMP3 (2008)
  • Author(s): Eguchi, T., S.Kubota, K.Kawata, Y.Mukudai, J.Uehara, T.Ohgawara, S.Ibaragi, A.Sasaki, T.Kuboki and M.Takigawa
  • Organizer: Fifth International Workshop on the CCN Family of Genes
  • Place of Presentation: Toronto、Canada
  • Year and Date: 20081000
• [Presentation] Roles of CCN2 in skeletal growth and regeneration -requirement for both endochondral and intramembranous bone formation (2008)
  • Author(s): Takigawa, M., N.Tomita, T.Hattori, H.Kawaki, S.Kubota, T.Kikuchi, S.Itoh, E.Aoyama, M.Yao, A.Suzuki, T.Maeda, K.Asaumi, T.Nishida, T.Ozaki, T.Yamashiro, K.M.Lyons, Y.Tabata
  • Organizer: Fifth International Workshop on the CCN Family of Genes
  • Place of Presentation: Toronto、Canada
  • Year and Date: 20081000
• [Presentation] Regulation of chondrocytic phenotype by micro RNA 18a : Involvement of Ccn/Ctgf as a major target gene (2008)
  • Author(s): Ohgawara, T., S.Kubota, H.Kawaki, S.Kondo, T.Eguchi, A.Sasaki, M.Takigawa
  • Organizer: Fifth International Workshop on the CCN Family of Genes
  • Place of Presentation: Toronto、Canada
  • Year and Date: 20081000
• [Presentation] Nucleophhosmin/B23 : A multifunctional regulator that determines the fate of ccn2 mRNA (2008)
  • Author(s): Kubota, S., Y.Mukudai, H.Kawaki, S.Kondo, T.Eguchi, K.Sumiyoshi, T.Ohgawara, T.Shimo, and M.Takigawa
  • Organizer: Fifth International Workshop on the CCN Family of Genes
  • Place of Presentation: Toronto、Canada
  • Year and Date: 20081000
• [Presentation] Novel transcription factor-like function of MMP-3/stromelys in-1 that regulates connective tissue growth factor (CCN2/CTGF) gene expression (2007)
  • Author(s): Eguchi, T., S.Kubota, Y.Mukudai, T.Yanagita, T.Ohgawara, J.Uehara and M.Takigawa
  • Organizer: The 29th Annual Meeting of the American Society for Bone and Mineral Research
  • Place of Presentation: Honolulu, U.S.A.
  • Year and Date: 20070900
• [Presentation] Effect of nicotine on CCN2/CTGF in human periodontal tissue (2007)
  • Author(s): Takeuchi, H., E.Murakashi, S.Kubota, M.Takigawa and Y.Numabe
  • Organizer: 11th Biennial Congress of the International Academy of Periodontology
  • Place of Presentation: Berne, Switzerland
  • Year and Date: 20070900
• [Book] Role of CCN2/CTGF/Hcs24 in Bone Growth.In ; International Review of Cytology (K.W. Jeon. ed)(Vol.147) (2007)
  • Author(s): Kubota, S. and M.Takigawa
  • Total Pages: 1-41
  • Publisher: Elsevier Inc.,San Diego
• [Remarks] Kubota, S. and M. Takigawa. 2007. CCN2 Molecule Page, UCSD/Nature. The Signaling Gateway. AfCS ID A003961
  • URL: http://www.signaling-gateway.org/molecule/query?afcsid=A003961
• [Remarks] Kubota, S. and M. Takigawa. 2007. CTGF. Atlas of Genetics and Cytogenetics in Oncology and Haematology. under editorial review
  • URL: http://AtlasGeneticsOncology.org/Genes/CTGFID40192ch6g23.html/