Creation of articular cartilage-specific bio-molecular imaging probe with potentials of dual modalities.

• Project/Area Number: 25670648
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Okayama University
• Principal Investigator: OOHASHI Toshitaka 岡山大学, 医歯(薬)学総合研究科, 教授 (50194262)
• Co-Investigator(Kenkyū-buntansha): NISHIDA Keiichiro 岡山大学, 大学院医歯薬学総合研究科, 准教授 (80284058) ; KAKUTA Hiroki 岡山大学, 大学院医歯薬学総合研究科, 准教授 (80362961)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プロテオグリカン / 変形性関節症 / X線 / 動物モデル / 創薬 / 軟骨 / 蛍光 / X線造影剤

Outline of Final Research Achievements

In the process of cartilage degeneration seen in osteoarthritis, loss of proteoglycan from articular cartilage has been widely accepted as a critical early event. We investigated bio-molecular imaging of articular cartilage using our molecular probes targeting articular GAGs.
Chondroitin sulfate, a major component of articular cartilage, has negative charge caused by sulfates. We designed lysine oligomers (monomer - pentamer) which were connected with the a-carboxyl and e-amino group. These lysine oligomers possess e-amino groups as cationic moieties. Then, we created a novel articular cartilage imaging X-ray probe Ke4-triiodobenzene (Ke4-TIB) and demonstrated an ex vivo imaging of articular cartilage in rat osteoarthritic models. The imaging could quantitate loss of proteoglycan from osteoarthritic cartilage. Ke4-TIB may have a potential of in vivo X-ray imaging in animal arthritic models in future, which contribute to drug discovery research for osteoarthritis.

Research Products

• [Journal Article] RXR Partial Agonist Produced by Side Chain Repositioning of Alkoxy RXR Full Agonist Retains Antitype 2 Diabetes Activity without the Adverse Effects (2015)
  • Author(s): Kawata et al.,
  • Journal Title: J Med Chem Volume: 58 Issue: 2 Pages: 912-926
  • DOI: 10.1021/jm501863r
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Light and electron microscopic detection of inflammation-targeting liposomes encapsulating high-density colloidal gold in arthritic mice. (2014)
  • Author(s): Maehara et al.
  • Journal Title: Inflammation Research Volume: 63 Pages: 139-147
  • Peer Reviewed
• [Journal Article] Design, synthesis, and preliminary ex vivo and in vivo evaluation of cationic magnetic resonance contrast agent for rabbit articular cartilage imaging. (2013)
  • Author(s): Irie T, Oda K, Shiino A, Kubo M, Morikawa S, Urushiyama N, Aonuma S, Kimura T, Inubushi T, Oohashi T, Komatsu N.
  • Journal Title: Med Chem Commun Volume: 4 Issue: 11 Pages: 1508-1512
  • DOI: 10.1039/c3md00229b
  • Peer Reviewed
• [Presentation] 新規X線造影剤による変形性膝関節症ラット関節軟骨の高解像度マイクロCT造影 (2014)
  • Author(s): 大橋俊孝、加来田博貴、芳谷学、大月孝志、大野充昭、山田翔也、前原亜美、廣畑聡、西田圭一郎、窪木拓男、二宮善文
  • Organizer: 第46回日本結合組織学会
  • Place of Presentation: ウインクあいち
  • Year and Date: 2014-06-05 – 2014-06-07
• [Presentation] リジンオリゴマープローブからなる関節軟骨特異的X線プローブの創出 (2014)
  • Author(s): 大橋俊孝、芳谷学、大野充昭、山田翔也、大月孝志、前原亜美、廣畑聡、西田圭一郎、窪木拓男、加来田博貴、二宮善文
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都府医師会館
• [Presentation] バイオイメージングを用いた関節軟骨の評価 (2013)
  • Author(s): 大橋俊孝、加来田博貴
  • Organizer: 日本臨床バイオメカニクス学会
  • Place of Presentation: 神戸国際会議場
  • Invited
• [Remarks] 岡山大学大学院医歯薬学総合研究科 分子医化学分野ホームページ
  • URL: http://www.okayama-u-mbb.jp/