Analysis of molecular mechanism of muscle heterotopic ossification by forming a network with CCN family proteins

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592732
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Okayama University
• Principal Investigator: NISHIDA Takashi 岡山大学, 医歯(薬)学総合研究科, 助教 (30322233)
• 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) ; KUBOTA Satoshi 岡山大学, 大学院医歯薬学総合研究科, 准教授 (90221936) ; HATTORI Takako 岡山大学, 大学院医歯薬学総合研究科, 助教 (00228488) ; AOYAMA Eriko 岡山大学, 大学院医歯薬学総合研究科, 助教 (10432650)
• Project Period (FY): 2011 – 2013
• Keywords: CCN2/CTGF / C2C12細胞 / 骨格筋分化 / 異所性骨化 / BMP2 / Ccn2欠損筋芽細胞

Research Abstract

The protein production of CCN2 (also known as Connective tissue growth factor) was increased in mouse myoblastic cell line C2C12 by treatment with tumor necrosis factor-a, which is produced upon inflammation. CCN2 promoted cell proliferation and the protein production of MyoD in C2C12 cells. Consistent with these findings, in vivo analyses with Ccn2-deficient skeletal muscle showed the decreased PCNA staining and muscle hypoplasia. Furthermore, bone morphogenetic protein (BMP)2-induced Runx2 and Osterix gene expression levels were significantly decreased in C2C12 cells co-treated with CCN2.

Research Products

• [Journal Article] CCN2 as a novel molecule supporting energy metabolism of chondrocytes (2014)
  • Author(s): Maeda-Uematsu, A., Kubota, S., Kawaki, H., Kawata, K., Miyake, Y., Hattori, T., Nishida, T., Moritani, N., Lyons, K. M., Iida, S., Takigawa, M.
  • Journal Title: J. Cell Biochem. Volume: 115 Pages: 854-865
  • DOI: 10.1002/jcb.24728
  • Peer Reviewed
• [Journal Article] The regenerative effects of CCN2 independent modules on chondrocytes in vitro and osteoarthritis models in vivo (2014)
  • Author(s): Abd El Kader, T., Kubota, S., Nishida, T., Hattori, T., Aoyama, E., Janune, D., Hara, E. S., Ono, M., Tabata, Y., Kuboki, T., Takigawa, M.
  • Journal Title: Bone Volume: 59 Pages: 180-188
  • DOI: 10.1016/j.bone.2013.11.010
  • Peer Reviewed
• [Journal Article] CCN family member 2/connective tissue growth factor (CCN2/CTGF) has anti-aging effects that protect articular cartilage from age-related degenerative changes (2013)
  • Author(s): Itoh, S., Hattori, T., Tomita, N., Aoyama, E., Yutani,Y., Yamashiro, T., Takigawa, M.
  • Journal Title: PLoS One Volume: 8 Pages: e71156
  • DOI: 10.1371/journal.pone.0071156.eCollection2013
  • Peer Reviewed
• [Journal Article] Regulation of CCN1 via the 3'-untranslated region (2013)
  • Author(s): Nakagawa, Y., Minato, M., Sumiyoshi, K., Maeda, A., Hara, C., Murase, Y., Nishida, T., Kubota, S., Takigawa, M.
  • Journal Title: J. Cell Commun. Signal. Volume: 7 Pages: 207-217
  • DOI: 10.1007/s12079-013-0202-x.Epub2013May16
  • Peer Reviewed
• [Journal Article] Cartilage–specific overexpression of CCN family member 2/connective tissue growth factor (CCN2/CTGF) stimulates insulin-like growth factor expression and bone growth (2013)
  • Author(s): Tomita, N., Hattori, T., Ito, S., Aoyama, E., Yao, M., Yamashiro, T., Takigawa M.
  • Journal Title: PLoS One Volume: 8 Pages: e59226
  • DOI: 10.1371/journal.pone.0059226.Epub2013Mar28
  • Peer Reviewed
• [Journal Article] Impaired glycolytic metabolism causes chondrocyte hypertrophy-like changes via promotion of phospho-Smad1/5/8 translocation into nucleus (2013)
  • Author(s): Nishida, T., Kubota, S., Aoyama, E., Takigawa, M.
  • Journal Title: Osteoarthritis Cartilage Volume: 21 Pages: 700-709
  • DOI: 10.1016/j.joca.2013.01.013.Epub2013Feb4
  • Peer Reviewed
• [Journal Article] Roles of heterotypic CCN2/CTGF-CCN3/NOV and homotypic CCN2-CCN2interactions in expression of the differentiated phenotype of chondrocytes (2012)
  • Author(s): Hoshijima, M., Hattori, T., Aoyama, E., Nishida, T., Yamashiro, T., Takigawa, M.
  • Journal Title: FEBS J. Volume: 279 Pages: 3584-3597
  • DOI: 10.1111/j.1742-4658.2012.08717.x.Epub2012Aug28
  • Peer Reviewed
• [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., Kubota, S., Eguchi, T., Aoyama, E., Moritani, N., Kondo, S., Nishida, T., Takigawa, M.
  • Journal Title: J. Cell Sci. Volume: 15 Pages: 2965-2972
  • DOI: 10.1242/jcs.101956.Epub2012Mar27
  • Peer Reviewed
• [Journal Article] Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes (2011)
  • Author(s): Nishida, T., Kubota, S., Aoyama, E., Janune, D., Maeda, A., Takigawa, M.
  • Journal Title: Endocrinology Volume: 152 Pages: 4232-4241
  • DOI: 10.1210/en.2011-0234.Epub2011Sep13
  • Peer Reviewed
• [Journal Article] Novel effects of CCN3 that may direct the differentiation of chondrocytes (2011)
  • Author(s): Janune, D., Kubota, S., Nishida, T., Kawaki, H., Perbal, B., Iida, S., Takigawa, M.
  • Journal Title: FEBS Lett. Volume: 585 Pages: 3033-3040
  • DOI: 10.1016/j.febslet.2011.08.024.Epub2011Aug23
  • Peer Reviewed
• [Presentation] 軟骨細胞における低出力超音波(LIPUS)とROCK阻害剤によるCCN2の相加的産生 (2014)
  • Author(s): 西田
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都
  • Year and Date: 20140228-0301
• [Presentation] マウス筋芽細胞においてCCN2はBMP2による骨芽細胞様変化を抑制する (2013)
  • Author(s): 西田
  • Organizer: 第55回歯科基礎医学会
  • Place of Presentation: 岡山
  • Year and Date: 20130920-22
• [Presentation] CCN2 is up-regulated in cultured chondrocytes treated with low-intensity plused ultrasound (LIPUS) (2013)
  • Author(s): Nishida
  • Organizer: 2nd joint meeting of IBMS-JSBMR
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20130528-0601
• [Presentation] 軟骨細胞におけるCCN2発現の低出力超音波(LIPUS)による誘導 (2013)
  • Author(s): 西田
  • Organizer: 第12回日本再生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20130321-23
• [Presentation] 軟骨細胞におけるCCN2発現の低出力超音波(LIPUS)による誘導 (2013)
  • Author(s): 西田
  • Organizer: 第26回日本軟骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 20130301-02
• [Presentation] 乳酸共存下での細胞内ATP量の減少は軟骨細胞の肥大化を引き起こす (2012)
  • Author(s): 西田
  • Organizer: 第54回歯科基礎医学会
  • Place of Presentation: 郡山
  • Year and Date: 20120914-16
• [Presentation] 乳酸共存下での細胞内ATP量の減少は軟骨細胞の肥大化を引き起こす (2012)
  • Author(s): 西田
  • Organizer: 第30回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 20120719-21
• [Presentation] CCN2/CTGFはBMP2による骨格筋内異所性骨化に協調的に作用する (2011)
  • Author(s): 西田
  • Organizer: 第53回歯科基礎医学会
  • Place of Presentation: 岐阜
  • Year and Date: 20111001-02
• [Presentation] CCN2/CTGFはBMP2による骨格筋内異所性骨化に協調的に作用する (2011)
  • Author(s): 西田
  • Organizer: 第4回日本CCNファミリー研究会
  • Place of Presentation: 岡山
  • Year and Date: 20110826-27
• [Presentation] 骨格筋内異所性骨化におけるCCN2/CTGFの作用 (2011)
  • Author(s): 西田
  • Organizer: 第29回日本骨代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 20110728-30
• [Remarks] 岡山大学歯学部口腔生化学分野ホームページ
  • URL: http://www.okayama-u.ac.jp/user/seika/index.html