A new protein transport system in cartilage: Multilayered transcytosis

• Project/Area Number: 23659872
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Okayama University
• Principal Investigator: TAKIGAWA Masaharu 岡山大学, 大学院・医歯薬学総合研究科, 教授 (20112063)
• Co-Investigator(Kenkyū-buntansha): 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) ; NISHIDA Takashi 岡山大学, 大学院・医歯薬学総合研究科, 助教 (30322233)
• Co-Investigator(Renkei-kenkyūsha): 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 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: LRP-1 / protein transport / transcytosis / CCN family / CCN2/CTGF / cartilage / トランスサートーシス / 軟骨 / タンパク質輸送 / 変異動物 / 骨格異常 / CTGF?CCN2 / トランスサイトーシス / 輸送

Research Abstract

Protein transportation in cartilage has been believed to be due to diffusion because there is no blood vessel in cartilage. In the present study, we revealed that low-density lipoprotein receptor-related protein-1(LRP-1) transports connective tissue growth factor/CCN family 2 (CTGF/CCN2/CCN2)in cartilage by transcytosis, indicating that this mechanism is a new protein transport system in cartilage. We also uncovered that cartilage-specific defect of LRP-1 resulted in skeletal disorders.

Research Products

• [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, and Takigawa M
  • Journal Title: Plos One Volume: 8(3)
  • NAID: 120005345532
  • 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,and Takigawa M
  • Journal Title: J Cell Sci Volume: 15 Pages: 2965-2972
  • Peer Reviewed
• [Journal Article] Roles of heterotypic CCN2/CTGF-CCN3/NOV and homotypic CCN2-CCN2 interactions 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(19) Pages: 3584-3597
  • NAID: 120005311985
  • 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
  • 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. and Takigawa, M.
  • Journal Title: J. Cell Sci. Volume: 未定
  • 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: 4232-41
  • Peer Reviewed
• [Presentation] CCN proteins in bone and cartilage. A Charles Perkinson Centre Symposium (2012)
  • Author(s): Takigawa M
  • Organizer: The CCN Proteins and Family of Genes and The IGF Binding Proteins - Health and Disease
  • Place of Presentation: Sydney、Australia
  • Year and Date: 2012-10-23
• [Presentation] 軟骨組織特異的低密度リポタンパク受容体欠損マウスにおける骨格形成 (2012)
  • Author(s): 河田かずみ、久保田聡、服部高子、青山絵理子、ジャヌネ ダニーロ、滝川正春
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] Role of the low-density lipoprotein receptor-related protein 1 in regulation of chondrocyte differentiation (2011)
  • Author(s): 河田かずみ
  • Organizer: 第32回岡山歯学会奨励論文賞受賞講演
  • Place of Presentation: 岡山
  • Year and Date: 2011-11-13
• [Presentation] The low-density lipoprotein receptor related protein 1 (LRP1) deficiency in the cartilage tissue leads to skeletal dysmorphisms (2011)
  • Author(s): Kawata K, Kubota S, Hattori T, Aoyama E, Janune D, Takigawa M
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Role of the low-density lipoprotein receptor related protein 1 (LRP1) in CCN2 protein transportation in chondrocytes. Cell Signaling Networks 2011: the 13th IUBMB Conference (2011)
  • Author(s): Kawata K, Kubota S, Eguchi T, Aoyama E, Kondo S, Hattori T, Takigawa M
  • Organizer: the 1st PABMB Conference and the 3rd Meetings of the Signal Transduction Branch & Oxidative Stress Branches of SMB. Merida
  • Place of Presentation: Yucatan, Mexico
• [Presentation] Role of the low-density lipoprotein receptor related protein 1 (LRP1) in CCN2 protein transportation in chondrocytes (2011)
  • Author(s): Kawata K, Kubota S, Eguchi T, Aoyama E, Kondo S, Hattori T, Takigawa M
  • Organizer: 第4回日本CCNファミリー研究会
  • Place of Presentation: 岡山
• [Presentation] 低密度リポタンパク受容体関連タンパ1(LRP1)による軟骨細胞でのCCNファミリー2/結合組織成長因子(CCN2/CTGF)タンパク質輸送 (2011)
  • Author(s): 河田かずみ、久保田聡、江口傑徳、青山絵理子、近藤誠二、滝川正春
  • Organizer: 第43回日本結合組織学会学術大会・第58回マトリックス研究会大会合同学術集会
  • Place of Presentation: 大分
• [Presentation] 低密度リポタンパク受容体関連タンパ1(LRP1)による軟骨細胞でのCCNファミリー2/結合組織成長因子（CCN2/CTGF）タンパク質輸送 (2011)
  • Author(s): 河田かずみ、久保田聡、 江口傑徳、 青山絵理子、 近藤誠二、 滝川正春
  • Organizer: 第43回日本結合組織学会学術大会・第58回マトリックス研究会大会合同学術集会
  • Place of Presentation: 大分
• [Remarks]
  • URL: http://www.dent.okayama-u.ac.jp/seika/index_sc_j.html
• [Remarks] 岡山大学歯学部の概要 口腔生化学分野
  • URL: http://www.dent.okayama-u.ac.jp/seika/index_sc_j.html