The International CCN Society

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President of the ICCNS Scientific Board

Masaharu Takigawa

Masaharu Takigawa, D.D.S., PhD.
Department of Biochemistry and Molecular Dentistry
Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
2-5-1, Shikata-cho, Okayama, 600-8525,
JAPAN
Tel: 81-86-235-6645
Fax: 81-86-235-6649
http://www.dent.okayama-u.ac.jp/seika/index_sc_e.html
takigawa@md.okayama-u.ac.jp

Present Position

Professor and Chair, Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Vice Director, Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Dental Center

Societies

  • The International CCN Society (First member)
  • International Bone and Mineral Society
  • Japanese Society of Cartilage Metabolism (board of directors)
  • Japanese Society for Bone and Mineral Metabolism (councilor, board of directors -2007)
  • Japanese Association for Oral Biology (councilor, board of directors -2006)
  • The Japanese Biochemical Society (councilor)
  • Japanese Society for Connective Tissue Research (councilor)
  • The Japanese Vascular Biology and Medicine Organization (councilor)
  • The Molecular Biology Society of Japan
  • The Japanese Cancer Association
  • Japan Society for Cell biology
  • American Society for Bone and Mineral Research
  • American Society for Biochemistry and Molecular Biology
  • American Association for Cancer Research

Awards

  • 1992 Scientific Award from Japanese Society for Bone and Mineral Metabolism
  • 1997 Promotion Award of Bone and Joint Disease from the Japan Rheumatism Foundation
  • 2012 International CCN Society Scientific Award

Editorial Boards

  • Journal of Cell Communication and Signaling
  • Journal of Oral Biosciences (Editor in Biochemistry)
  • Journal of Orthopaedic Science (Editorial board)
  • Journal of Bone and Mineral Metabolism (Advisory board)

Current Research

  • The roles of CCN proteins in skeletal growth and regeneration
  • CCN2 actions in angiogenesis and tumor growth
  • Skeletal Biology

Selected Recent Publications

  • Itoh S, Hattori T, Tomita N, Aoyama E, Yutani Y, Yamashiro T, Takigawa M.
    CCN family member 2/connective tissue growth factor (CCN2/CTGF) has anti-aging effects that protect articular cartilage from age-related degenerative changes.
    PLoS One. 2013 Aug 12;8(8):e71156.
  • Takigawa M.
    CCN2: a master regulator of the genesis of bone and cartilage.
    J Cell Commun Signal. 2013 Aug;7(3):191-201.
  • Nakagawa Y, Minato M, Sumiyoshi K, Maeda A, Hara C, Murase Y, Nishida T, Kubota S, Takigawa M.
    Regulation of CCN1 via the 3'-untranslated region.
    J Cell Commun Signal. 2013 Aug;7(3):207-17.
  • Tomita N, Hattori T, Itoh S, Aoyama E, Yao M, Yamashiro T, Takigawa M.
    Cartilage-specific over-expression of CCN family member 2/connective tissue growth factor (CCN2/CTGF) stimulates insulin-like growth factor expression and bone growth.
    PLoS One. 2013;8(3):e59226.
  • Sumiyoshi K, Kubota S, Ohgawara T, Kawata K, Abd El Kader T, Nishida T, Ikeda N, Shimo T, Yamashiro T, Takigawa M.
    Novel role of miR-181a in cartilage metabolism.
    J Cell Biochem. 2013 Sep;114(9):2094-100.
  • Nishida T, Kubota S, Aoyama E, Takigawa M.
    Impaired glycolytic metabolism causes chondrocyte hypertrophy-like changes via promotion of phospho-Smad1/5/8 translocation into nucleus.
    Osteoarthritis Cartilage. 2013 May 21(5):700-9.
  • Aoyama E, Kubota S, Takigawa M.
    CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling.
    FEBS Lett. 2012 Dec 14;586(24):4270-5.
  • Abd El Kader T, Kubota S, Janune D, Nishida T, Hattori T, Aoyama E, Perbal B, Kuboki T, Takigawa M.
    Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family.
    J Cell Commun Signal. 2013 Mar;7(1):11-8.
  • Honjo T, Kubota S, Kamioka H, Sugawara Y, Ishihara Y, Yamashiro T, Takigawa M, Takano-Yamamoto T.
    Promotion of Ccn2 expression and osteoblastic differentiation by actin polymerization, which is induced by laminar fluid flow stress.
    J Cell Commun Signal. 2012 Dec;6(4):225-32.
  • Hoshijima M, Hattori T, Aoyama E, Nishida T, Yamashiro T, Takigawa M.
    Roles of heterotypic CCN2/CTGF-CCN3/NOV and homotypic CCN2-CCN2 interactions in expression of the differentiated phenotype of chondrocytes.
    FEBS J. 2012 Oct;279(19):3584-97.
  • Furumatsu T, Kanazawa T, Miyake Y, Kubota S, Takigawa M, Ozaki T.
    Mechanical stretch increases Smad3-dependent CCN2 expression in inner meniscus cells.
    J Orthop Res. 2012 Nov;30(11):1738-45.
  • Kawata K, Kubota S, Eguchi T, Aoyama E, Moritani NH, Kondo S, Nishida T, Takigawa M.
    Role of LRP1 in transport of CCN2 protein in chondrocytes.
    J Cell Sci. 2012 Jun 15;125(Pt 12):2965-72.
  • Nishida T, Kubota S, Aoyama E, Janune D, Maeda A, Takigawa M.
    Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes.
    Endocrinology. 2011 Nov;152(11):4232-41.
  • Janune D, Kubota S, Nishida T, Kawaki H, Perbal B, Iida S, Takigawa M.
    Novel effects of CCN3 that may direct the differentiation of chondrocytes.
    FEBS Lett. 2011 Oct 3;585(19):3033-40.
  • Kawaki H, Kubota S, Suzuki A, Suzuki M, Kohsaka K, Hoshi K, Fujii T, Lazar N, Ohgawara T, Maeda T, Perbal B, Takano-Yamamoto T, Takigawa M.
    Differential roles of CCN family proteins during osteoblast differentiation: Involvement of Smad and MAPK signaling pathways.
    Bone. 2011 Nov;49(5):975-89.
  • Miyake Y, Furumatsu T, Kubota S, Kawata K, Ozaki T, Takigawa M.
    Mechanical stretch increases CCN2/CTGF expression in anterior cruciate ligament-derived cells.
    Biochem Biophys Res Commun. 2011 Jun 3;409(2):247-52.
  • Janune D, Kubota S, Lazar N, Perbal B, Iida S, Takigawa M.
    CCN3-mediated promotion of sulfated proteoglycan synthesis in rat chondrocytes from developing joint heads.
    J Cell Commun Signal. 2011 Aug;5(3):167-71.
  • Ohgawara T, Kubota S, Kawaki H, Kurio N, Abd El Kader T, Hoshijima M, Janune D, Shimo T, Perbal B, Sasaki A, Takigawa M.
    Association of the metastatic phenotype with CCN family members among breast and oral cancer cells.
    J Cell Commun Signal. 2011 Dec;5(4):291-9.
  • Kubota S and Takigawa M.
    The role of CCN2 in cartilage and bone development.
    J Cell Commun Signal. 2011 Aug;5(3):209-17.
  • Kubota S. and Takigawa M.
     CCN. Encyclopedia of Signaling Molecules (Choi S. ed.), Springer, 2010, in press
  • Nishida T, Emura K, Kubota S, Lyons KM, Takigawa M.
    CCN family 2/connective tissue growth factor (CCN2/CTGF) promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein (DC-STAMP). 
    J. Bone Miner. Res., 2010 Aug 18. [Epub ahead of print]
  • Mukudai Y, Kubota S, Eguchi T, Sumiyoshi K, Janune D, Kondo S, Shintani S, Takigawa M.
    A coding RNA segment that enhances the ribosomal recruitment of chicken ccn1 mRNA. 
    J. Cell. Biochem. 2010;111:1607-18
  • Sumiyoshi K, Kubota S, Ohgawara T, Kawata K, Nishida T, Shimo T, Yamashiro T, Takigawa M. 
    Identification of miR-1 as an miRNA that supports late-stage differentiation of growth cartilage cells.
    Biochem. Biophys. Res. Commun., 2010;402:286-90
  • Perbal A. Takigawa M, Perbal B. 
    CCN Proteins in Health and Diseases,
    Springer, Dordrecht, 2010, pp.1-338
  • Kawaki H, Kubota S, Aoyama E, Fujita N, Hanagata H, Miyauchi A, Nakai K, Takigawa M.  Design and utility of CCN2 anchor peptide aptamers. 
    Biochimie. 2010;92:1010-5
  • Takeuchi H, Kubota S, Murakashi E, Zhou Y, Endo K, Ng PS, Takigawa M, Numabe Y. 
    Nicotine-induced CCN2: from smoking to periodontal fibrosis. 
    J. Dent Res. 2010;34-9.
  • Sumiyoshi K, Kubota, S, Furuta, RA, Tasui K, Aoyama, E, Kawaki H, Kawata, K, Ohgawara T, Yamashiro T, Takigawa M. 
    Thrombopoietic-mesenchymal interaction that may facilitate both endochondral ossification and pletelet maturation via CCN2. 
    J. Cell Commun. Signal. 2010;4:5-14.
  • Aoyama E, Hattori T, Hoshijima M, Araki D, Nishida T, Kubota S, Takigawa M.
    N-terminal domains of CCN protein 2/connective tissue growth factor bind to aggrecan. 
    Biochem. J. 2009;420:413-420.
  • Sakai Y, Balam TA, Kuroda S, Tamamura N, Fukunaga T, Takigawa M, Takano-Yamamoto T.
    CTGF and apoptosis in mouse osteocytes induced by tooth movement. 
    J. Dent. Res. 2009;88:345-50.
  • Ohgawara, T., Kubota, S., Kawaki, H., Kondo, S., Eguchi, T., Kurio, N., Aoyama, E., Sasaki, A. Takigawa, M.
    Regulation of chondrocytic phenotype by micro RNA 18a: Involvement of Ccn2/Ctgf as a major target gene.
    FEBS Lett. 2009;583:1006-10.
  • Maeda, A., Nishida, T., Aoyama, E., Kubota, S., Lyons, K. M., Kuboki, T., Takigawa, M.
    CCN family 2/connective tissue growth factor modulates BMP signaling as a signal conductor, which action regulayes the proliferation and differentiation of chondrocytes. 
    J. Biochem. 2009;145:207-16.
  • Nishida, T. Kondo, S., Maeda, A., Kubota, S., Lyons, K. M., Takigawa, M.
    CCN family 2/connective tissue growth factor (CCN2/CTGF) regulates the expression of Vegf through Hif-1a expression in a chondrocytic cell line, HCS-2/8, under hypoxic condition.
    Bone  2009;44:24-31.
  • Takeuchi, H., Kubota, S., Murakashi, E., Fukada, T., Hashimoto, S., Takigawa, M. and Numabe, Y. 
    Effect of TGF-β1 on CCN2/CTGF in normal human gingival fibroblasts and periodontal ligament cells.
    J. periodontal. Res., 2009;44:161-169. 
  • Mukudai, Y., Kubota, S., Kawaki, H., Kondo, S. Eguchi, T., Sumiyoshi, K., Ohgawara, T., Shimo, T., Takigawa, M. 
    Post-transcriptional regulation of chicken ccn2 gene expression by nucleophosmin/B23 during chondrocyte differentiation.
    Mol. Cell Biol. 2008;28:6134-47.
  • Kawaki H , Kubota S, Suzuki A, Lazar N, Yamada T, Matsumura T, Ohgawara T, Maeda T, Perbal B, Lyons K, Takigawa M
    Cooperative regulation of chondrocyte differentiation by CCN2 and CCN3 revealed by a comprehensive analysis of the CCN family proteins in cartilage
    J. Bone Miner. Res. 2008;23:1751-64.
  • Eguchi T, Kubota S, Kawata K, Mukudai Y, Uehara J, Ohgawara T, Ibaragi S, Sasaki S, Kuboki T, and Takigawa M
    Novel transcription factor-like function of human MMP3 regulating CTGF/CCN2 gene
    Mol. Cell. Biol. 2008;28:2391-413.
  • Kikuchi T, Kubota, S, Asaumi K, Kawaki H, Nishida T, Kawata K, Mitani S, Tabata Y, Ozaki T, and Takigawa M
    Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel
    Tissue Eng. Part A 2008;14:1089-98
  • Ono M, Kubota S, Fujisawa T, Sonoyama W, Kawaki H, Akiyama K, Oshima M, Nishida T, Yoshida Y, Suzuki K, Takigawa M, and Kuboki T
    Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2.
    Cell Transplantation 2008;17:231-40.
  • Fujisawa T, Hattori T, Ono M, Uehara J, Kubota, S, Kuboki T, and Takigawa M
    CCN family 2 / Connective tissue growth factor (CCN2/CTGF) stimulates proliferation and differentiation of auricular chondrocytes.
    Osteoarthritis Cartilage 2008;16:787-95
  • Kawaki H, Kubota S, Suzuki A, Yamada T, Matsumura T, Mandai T, Yao M, Maeda T, Lyons KM, Takigawa M.
    Functional requirement of CCN2 for intramembranous bone formation in embryonic mice.
    Biochem. Biophys. Res. Commun. 2008;366:450-6.
  • Oka M, Kubota S, Kondo S, Eguchi T, Kuroda C, Kawata K, Minagi S, Takigawa M.
    Gene expression and distribution of connective tissue growth factor (CCN2/CTGF) during secondary ossification center formation.
    J. Histochem. Cytochem. 2007;55:1245-55.
  • Koitabashi N, Arai M, Niwano K, Watanabe A, Endoh M, Suguta M, Yokoyama T, Tada H, Toyama T, Adachi H, Naito S, Oshima S, Nishida T, Kubota S, Takigawa M, and Kurabayashi M
    Plasma connective tissue growth factor is a novel potential biomarker of cardiac dysfunction in patients with chronic heart failure.
    Eur. J. Heart Fail. 2008;10:373-9.
  • Kubota S, and Takigawa M
    Role of CCN2/CTGF/Hcs24 in Bone Growth.
    Int. Rev. Cytol. 2007; 147: 1-41. Review.
  • Kubota S, and Takigawa M
    CCN2 Molecule Page UCSD/Nature. The Signaling Gateway. 2007; AfCS ID A003961:
    URL:
    http://www.signaling-gateway.org/molecule/query?afcsid=A003961
  • Kubota S, and Takigawa M
    CTGF (connective tissue growth factor). Atlas Genet Cytogenet Oncol Haematol. 2007; CTGFID40192.
    URL:
    http://AtlasGeneticsOncology.org/Genes/CTGFID40192ch6q23.html
  • Kubota S, Takigawa M.
    CCN family proteins and angiogenesis: from embryo to adulthood.
    Angiogenesis. 2007;10:1-11. Review.
  • Kubota S, Yeger H, Perbal B, Takigawa M.
    Report on the fourth international workshop on the CCN family of genes.
    J. Cell Commun. Signal. 2007 Jun;1:59-65.
  • Miyamoto Y, Mabuchi A, Shi D, Kubo T, Takatori Y, Saito S, Fujioka M, Sudo A, Uchida A, Yamamoto S, Ozaki K, Takigawa M, Tanaka T, Nakamura Y, Jiang Q, Ikegawa S.
    A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis.
    Nat. Genet. 2007; 39:529-33. Epub 2007 Mar 25.
  • Eguchi T, Kubota S, Kawata K, Mukudai Y, Ohgawara T, Miyazono K, Nakao K, Kondo S, and Takigawa M
    Different transcriptional strategies of ccn2/ctgf gene induction between human chondrocytic and breast cancer cell lines.
    Biochimie, 2007; 89: 278-288
  • Yanagita T, Kubota S, Kawata K, Kawaki H, Kondo S, Takano-Yamamoto T, Tanaka S. and Takigawa M
    Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes
    FEBS J. 2007; 274:1655-1665.
  • Koitabashi N, Arai M, Kogure S, Niwano K, Watanabe A, Aoki Y, Maeno T, Nishida T, Kubota S, Takigawa M, and Kurabayashi M
    Increased connective tissue growth factor relative to brain natriuretic peptide as a determinant of myocardial fibrosis.
    Hypertension 2007; 49:1120-1127.
  • Ono M, Kubota S, Fujisawa T, Sonoyama W, Kawaki H, Akiyama K, Oshima M, Nishida T, Yoshida Y, Suzuki K, Takigawa M, Kuboki T.
    Promotion of attachment of human bone marrow stromal cells by CCN2.
    Biochem. Biophys. Res. Commun. 2007;357(1):20-5.
  • Nishida T, Kawaki H, Baxter RM, Deyoung RA, Takigawa M, Lyons KM.
    CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes.
    J. Cell Commun. Signal. 2007 ;1(1):45-58.
  • Kondo S, Kubota S, Moritani N, Yosimichi G, Nishida T, Matsushita H, Matsumoto S, Kitoh T, Nakao K, Sugahara T, and Takigawa M
    Hypoxic Regulation of Stability of Connective tissue growth factor/CCN2 mRNA by 3'-untranslated region interacting with a cellular protein in human chondrosarcoma cells.
    Oncogene 2006; 25:1099-1110.
  • Shimo T, Kubota S, Eguchi T, Ibaragi S, Isowa S, Yoshioka N, Sasaki A, and Takigawa M
    Pathogenic role of connective tissue growth factor (CCN2/CTGF) in osteolytic metastasis of breast cancer.
    J. Bone Miner. Res. 2006; 21:1045-1059.
  • Yosimichi G, Kubota S, Nishida T, Kondo S, Yanagita T, Nakao K, Takano-Yamamoto T, and Takigawa M
    Roles of PKC, PI3K and JNK in multiple transduction of CCN2/CTGF signals in chondrocytes.
    Bone 2006; 38:853-863.
  • Kondo S, Tanaka N, Kubota S, Mukudai Y, Yosimichi G, Sugahara T, and Takigawa M
    Novel angiogenic inhibitor DN-9693 that inhibits post-transcriptional induction of connective tissue growth factor (CTGF/CCN2) by vascular endothelial growth factor (VEGF) in human endothelial cells.
    Mol. Cancer Ther. 2006; 5:129-137.
  • Perbal, B. and Takigawa, M. (Editors)
    CCN Proteins : A New Family of Cell Growth and Differentiation Regulators. Imperial College Press, London, 2005, 1-311
  • Mukudai Y, Kubota S, Eguchi T, Kondo S, Nakao K, Takigawa M.
    Regulation of chicken ccn2 gene by interaction between RNA cis-element and putative trans-factor during differentiation of chondrocytes.
    J. Biol. Chem. 2005;280(5):3166-77. Epub 2004 Nov 18.
  • Nishida T, Kubota S, Kojima S, Kuboki T, Nakao K, Kushibiki T, Tabata Y, Takigawa M.
    Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).
    J. Bone Miner. Res. 2004;19(8):1308-19.
  • Yokoi H, Mukoyama M, Nagae T, Mori K, Suganami T, Sawai K, Yoshioka T, Koshikawa M, Nishida T, Takigawa M, Sugawara A, Nakao K.
    Reduction in connective tissue growth factor by antisense treatment ameliorates renal tubulointerstitial fibrosis.
    J. Am .Soc. Nephrol. 2004 Jun;15(6):1430-40.
  • Takigawa M, Nakanishi T, Kubota S, Nishida T.
    The role of CTGF/Hcs24/ecogenin in skeletal growth control.
    J. Cell. Physiol. 2003;194(3):256-66. Review.
  • Takigawa M
    CTGF/Hcs24 as a multifunctional growth factor for fibroblasts, chondrocytes, and vascular endothelial cells.
    Drug News Perspect. 2003;16(1):11-21. Review.