Analyses on a molecular mechanism of spontaneous articular cartilage regeneration induced in vivo by double-network gel

2010 Fiscal Year Final Research Report

• Project/Area Number: 20240045
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Hokkaido University
• Principal Investigator: YASUDA Kazunori Hokkaido University, 大学院・医学研究科, 教授 (20166507)
• Co-Investigator(Kenkyū-buntansha): OHMIYA Yoshihiro 産業技術総合研究所, 副研究部門長 (20223951) ; KITAMURA Nobuto 北海道大学, 大学院・医学研究科, 講師 (80447044) ; ONODERA Shin 北海道大学, 大学院・医学研究科, 客員准教授 (00359481) ; KWON Hyuck Joon 北海道大学, 大学院・医学研究科, 特任助教 (20455629) ; KUROKAWA Takayuki 北海道大学, 大学院・先端生命科学研究院, 特任助教 (40451439)
• Co-Investigator(Renkei-kenkyūsha): OSADA Yoshihito 理化学研究所, 基幹研究所, 副所長 (60007804) ; GONG Jian Ping 北海道大学, 大学院・先端生命科学研究院, 教授 (20250417)
• Project Period (FY): 2008 – 2010
• Keywords: 関節軟骨 / 自然再生 / 再生誘導材料 / ダブルネットワークゲル / 分子機序

Research Abstract

(1) We clarified genetic characteristics of the articular cartilage spontaneously regenerated by double-network (DN) gel, using microarray. (2) We found that PAMPS, a component of the DN gel, has an ability that can induces the spontaneous articular cartilage regeneration. (3) We observed marker genes in a chondrogenic differentiation process, using multi-colored bioluminescence probes. We discovered a synchronized oscillation phenomenon of cell metabolism in prechondrogenic condensation. (4) We developed the transgenic bioluminescence mouse to be used for in vivo imaging. (5) These results provided important information to clarify a comprehensive mechanism of the spontaneous cartilage regeneration phenomenon.

Research Products

• [Journal Article] Robust bonding and one-step facile synthesis of tough hydrogels with desirable shape by virtue of the double network structure (2011)
  • Author(s): Saito J, Furukawa H, Kurokawa T, Kuwabara R, Kuroda S, Hu J, Tanaka Y, Gong JP, Kitamura N, Yasuda Y
  • Journal Title: Polym Chem 2 Pages: 575-580, doi:10.1039/C0PY00272K
  • URL: http://pubs.rsc.org
  • Peer Reviewed
• [Journal Article] Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel (2011)
  • Author(s): Yokota M, Yasuda K, Kitamura N, Arakaki K, Onodera S, Kurokawa T, Gong JP
  • Journal Title: BMC Musculoskeletal Disorders 12:49 Pages: doi:10.1186/1471-2474-12-49
  • URL: http://www.biomedcentral.com/1471-2474/12/49
  • Peer Reviewed
• [Journal Article] In vivo effects of isolated implantation of salmon-derived crosslinked atelocollagen sponge into an osteochondral defect (2011)
  • Author(s): Kawaguchi Y, Kondo E, Kitamura N, Arakaki K, Tanaka Y, Munekata M, Nagai N, Yasuda K
  • Journal Title: J Mater Sci Mater Med 22(2) Pages: 397-404
  • Peer Reviewed
• [Journal Article] Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation (2011)
  • Author(s): Arakaki K, Kitamura N, Kurokawa T, Onodera S, Kanaya F, Gong JP, Yasuda K
  • Journal Title: J Mater Sci Mater Med 22(2) Pages: 417-425
  • Peer Reviewed
• [Journal Article] Induction of Spontaneous Hyaline Cartilage Regeneration Using a Double-Network Gel : Efficacy of a Novel Therapeutic Strategy for an Articular Cartilage Defect (2011)
  • Author(s): Kitamura N, Yasuda K, Ogawa M, Arakaki K, Kai S, Onodera S, Kurokawa T, Gong JP
  • Journal Title: Am J Sports Med (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] In vitro differentiation of chondrogenic ATDC5 cells is enhanced by culturing on synthetic hydrogels with various charge densities (2010)
  • Author(s): Kwon HJ, Yasuda K, Ohmiya Y, Honma KI, Chen YM, Gong JP
  • Journal Title: Acta Biomater 6(2) Pages: 494-501
  • Peer Reviewed
• [Journal Article] Implantation of autogenous meniscal fragments wrapped with a fascia sheath enhances fibrocartilage regeneration in vivo in a large harvest site defect (2010)
  • Author(s): Kobayashi Y, Yasuda K, Kondo E, Katsura T, Tanabe Y, Kimura M, Tohyama H.
  • Journal Title: Am J Sports Med 38(4) Pages: 740-8
  • Peer Reviewed
• [Journal Article] Artificial cartilage made from a novel double-network hydrogel : In vivo effects on the normal cartilage and ex vivo evaluation of the friction property (2010)
  • Author(s): Arakaki K, Kitamura N, Fujiki H, Kurokawa T, Iwamoto M, Ueno M, Kanaya F, Osada Y, Gong JP, Yasuda K
  • Journal Title: J Biomed Mater Res A 93(3) Pages: 1160-1168
  • Peer Reviewed
• [Journal Article] Bioluminescence imaging of dual gene expression at the single-cell level (2010)
  • Author(s): Kwon HJ, Enomoto T, Shimogawara M, Yasuda K, Nakajima Y, Ohmiya Y
  • Journal Title: BioTechniques 48(6) Pages: 460-462
  • Peer Reviewed
• [Journal Article] Gene expression, glycocalyx assay, and surface properties of human endothelial cells cultured on hydrogel matrix with sulfonic moiety : Effect of elasticity of hydrogel (2010)
  • Author(s): Yang JJ, Chen YM, Kurokawa T, Gong JP, Onodera S, Yasuda K
  • Journal Title: Journal of Biomedical Materials Research : Part A 95(2) Pages: 531-42
  • Peer Reviewed
• [Journal Article] Study on the sliding friction of endothelial cells cultured on hydrogel and the role of glycocalyx on friction reduction (2010)
  • Author(s): Chen YM, Kurokawa T, Tominaga T, Yasuda K, Osada Y, Gong JP, Yamamoto K, Ando J
  • Journal Title: Advanced Engineering Materials 12(11) Pages: B628-B636
  • Peer Reviewed
• [Journal Article] Tuning of cell proliferation on tough gels by critical charge effect (2009)
  • Author(s): Chen YM, Gong JP, Tanaka M, Yasuda K, Yamamoto S, Shimomura M, Osada Y
  • Journal Title: J Biomed Mater Res : Part A 88(1) Pages: 74-83
  • Peer Reviewed
• [Journal Article] A novel double-network hydrogel induces spontaneous articular cartilage regeneration in vivo in a large osteochondral defect (2009)
  • Author(s): Yasuda K, Kitamura N, Gong JP, Arakaki K, Kwon HJ, Onodera S, Chen YM, Kurokawa T, Kanaya F, Ohmiya Y, Osada Y
  • Journal Title: Macromol Biosci 9(4) Pages: 307-316
  • Peer Reviewed
• [Journal Article] In vivo bioluminescence imaging of bone marrow-derived cells in brain inflammation (2009)
  • Author(s): Akimoto H, Kwon HJ, Ozaki M, Yasuda K, Honma K, Ohmiya Y
  • Journal Title: Biochemical and Biophysical Research Communications 380(4) Pages: 844-849
  • Peer Reviewed
• [Journal Article] Biological responses of novel high-toughness double network hydrogels in muscle and the subcutaneous tissues (2008)
  • Author(s): Tanabe Y, Yasuda K, Azuma C, Taniguro H, Onodera S, Suzuki A, Chen YM, Gong JP, Osada Y
  • Journal Title: J Mater Sci Mater Med 19(3) Pages: 1379-1387
  • Peer Reviewed
• [Journal Article] Gene expression profile of rabbit cartilage by expressed sequence tag analysis (2008)
  • Author(s): Kwon HJ, Akimoto H, Ohmiya Y, Honma K, Yasuda K
  • Journal Title: Gene 424(1-2) Pages: 147-152
  • Peer Reviewed
• [Presentation] Gene profiles of the regenerated cartilage tissue induced by implantation of a novel double-network hydrogel (2010)
  • Author(s): Imabuchi R, Kwon HJ, Kitamura N, Kurokawa T, Gong JP, Ohmiya Y, Yasuda K
  • Organizer: 9th World Congress of the International Cartilage Repair Society, Sitges
  • Place of Presentation: Spain
  • Year and Date: 20100926-20100929
• [Presentation] A Negatively Charged PAMPS Gel Component Plays A Significant Role in The InVivo Spontaneous Cartilage Regeneration Induced by Implantation of PAMPS/PDMAAm Double-network Gel (2010)
  • Author(s): Ogawa M, Kitamura N, Arakaki K, Onodera S, Kurokawa T, Gong JP, Tanaka Y, Takakura Y, Yasuda K
  • Organizer: 56th Annual Meeting of the Orthopaedic Research Society
  • Place of Presentation: New Orleans, Louisiana
  • Year and Date: 20100306-20100309
• [Patent(Industrial Property Rights)] 骨充填型軟骨組織再生誘導剤 (2009)
  • Inventor(s): 安田和則、長田義仁、〓剣萍、北村信人
  • Industrial Property Rights Holder: 国立大学法人 北海道大学
  • Industrial Property Number: 特許,PCT/JP2009/64888(特願2008-217253)
  • Filing Date: 2009-08-26