Preclinical study to elucidate molecular mechanism of matrix anchoring using bacterial proteins

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bacteriology (including Mycology)
• Research Institution: Okayama University (2012-2013); Kitasato University (2011)
• Principal Investigator: MATSUSHITA Osamu 岡山大学, 医歯(薬)学総合研究科, 教授 (00209537)
• Co-Investigator(Kenkyū-buntansha): ADACHI Eijiro 北里大学, 医学(系)研究科(研究院), 教授 (30110430) ; INOUE Jo 京都大学, 医学(系)研究科(研究院), 助教 (00433714) ; MORI Nozomu 香川大学, 医学部, 教授 (90124883) ; UCHIDA Kentaro 北里大学, 医学部, 助教 (50547578)
• Co-Investigator(Renkei-kenkyūsha): MIMA Takehiko 岡山大学, 医歯(薬)学総合研究科, 助教 (80596437) ; MIYASHITA Takenori 香川大学, 医学部, 助教 (60363214)
• Project Period (FY): 2011 – 2013
• Keywords: 細菌毒素 / コラーゲン結合ドメイン / 細胞外マトリックス / 膠原線維 / アンカーリング / 骨新生 / 再生医療 / 技術移転

Research Abstract

Flesh-eating bacteria produce collagenases, enzymes to degrade tissue collagen fibrils. The enzyme possesses a collagen-binding domain(s). Although its molecular size is small, the domain forms sandwich-like structure to bind to untwisted region of triple-helical collagen molecule. Meanwhile, human growth factor accelerates cell growth. Various growth factors were fused with the domain to anchor them on tissue collagen fibrils, demineralized bone matrix, or collagen sheet/particles. Using these novel materials, osteogenesis or angiogenesis was successfully induced.

Research Products

• [Journal Article] Direct cytocidal effect of galectin-9 localized on collagen matrices on human immune cell lines (2014)
  • Author(s): Fukata Y, Itoh A, Nonaka Y, Ogawa T, Nakamura T, MatsushitaO, Nishi N
  • Journal Title: Biochim Biophys Acta Volume: 1840(6) Pages: 1892-1901
  • DOI: 10.1016/j.bbagen.2014.01.019
  • Peer Reviewed
• [Journal Article] Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model (2014)
  • Author(s): Katikaneni R, Ponnapakkam T, MatsushitaO, Sakon J, Gensure R
  • Journal Title: Anticancer Drugs Volume: 25(1) Pages: 30-38
  • DOI: 10.1097/CAD.0b013e3283650bff
  • Peer Reviewed
• [Journal Article] Acceleration of bone formation during fracture healing by injectable collagen powder and human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase (2013)
  • Author(s): Saito W, Uchida K, Ueno M, MatsushitaO, Inoue G, Nishi N, Ogura T, Hattori S, Fujimaki H, Tanaka K, Takaso M
  • Journal Title: J Biomed Mater Res A
  • DOI: 10.1002/jbm.a.34974
  • Peer Reviewed
• [Journal Article] Acceleration of periosteal bone formation by human basic fibroblast growth factor containing a collagen-binding domain from Clostridium histolyticum collagenase (2013)
  • Author(s): Uchida K, Matsushita O, Naruse K, Mima T, Nishi N, Hattori S, Ogura T, Inoue G, Tanaka K, Takaso M
  • Journal Title: J Biomed Mater Res A
  • DOI: 10.1002/jbm.a.34841
  • Peer Reviewed
• [Journal Article] Effects of CB-VEGF-A injection in rat flap models for improved survival (2013)
  • Author(s): Sakamoto K, Hattori M, Kounoike N, Uchinuma E. Akimoto M, Takeda A, MatsushitaO, Inoue J
  • Journal Title: Plast Reconstr Surg Volume: 131(4) Pages: 717-725
  • DOI: 10.1097/PRS.0b013e3182818b34
  • Peer Reviewed
• [Journal Article] Structural comparison of ColH and ColG collagen-binding domains from Clostridium histolyticum (2013)
  • Author(s): Bauer R, Wilson JJ, Philominathan ST, Davis D, MatsushitaO, Sakon J
  • Journal Title: J Bacteriol Volume: 195(2) Pages: 318-327
  • DOI: 10.1128/JB.00010-12
  • Peer Reviewed
• [Journal Article] Bacterial collagen-binding domain targets undertwisted regions of collagen (2012)
  • Author(s): Philominathan ST, Koide T, MatsushitaO, Sakon J
  • Journal Title: Protein Sci Volume: 21(10) Pages: 1554-1565
  • DOI: 10.1002/pro.2145
  • Peer Reviewed
• [Journal Article] A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice (2012)
  • Author(s): Ponnapakkam T, Katikaneni R, Suda H, Miyata S, MatsushitaO, Sakon J, Gensure RC
  • Journal Title: Calcif Tissue Int Volume: 91(3) Pages: 196-203
  • DOI: 10.1007/s00223-012-9626-1
  • Peer Reviewed
• [Journal Article] Probing the 3-D structure, dynamics, and stability of bacterial collagenase collagen binding domain (apo- versus holo-) by limited proteolysis MALDI-TOF MS (2012)
  • Author(s): Sides CR, Liyanage R, Lay JO Jr, Philominathan ST, Matsushita O, Sakon J
  • Journal Title: J Am Soc Mass Spectrom Volume: 23(3) Pages: 505-519
  • DOI: 10.1007/s13361-011-0309-3
  • Peer Reviewed
• [Journal Article] Treatment for chemotherapy-induced alopecia in mice using parathyroid hormone agonists and antagonists linked to a collagen binding domain (2012)
  • Author(s): Katikaneni R, Ponnapakkam T, Suda H, Miyata S, Sakon J, MatsushitaO, Gensure RC
  • Journal Title: Int J Cancer Volume: 131(5) Pages: E813-821
  • DOI: 10.1002/ijc.27379
  • Peer Reviewed
• [Journal Article] Prevention of chemotherapy-induced osteoporosis by cyclophosphamide with a long-acting form of parathyroid hormone (2011)
  • Author(s): Ponnapakkam T, Katikaneni R, Nichols T, Tobin G, Sakon J, Matsushita O, Gensure RC
  • Journal Title: J Endocrinol Invest Volume: 34(11) Pages: e392-397
  • DOI: 10.3275/7864
  • Peer Reviewed
• [Journal Article] Monthly administration of a novel PTH-collagen binding domain fusion protein is anabolic in mice (2011)
  • Author(s): Ponnapakkam T, Katikaneni R, Miller E, Ponnapakkam A, Hirofumi S, Miyata S, Suva LJ, Sakon J, Matsushita O, Gensure RC
  • Journal Title: Calcif Tissue Int Volume: 88(6) Pages: 511-520
  • DOI: 10.1007/s00223-011-9485-1
  • Peer Reviewed
• [Presentation] Drug delivery based on clostridial collagenase showed therapeutic effects in orthopedic surgery (2014)
  • Author(s): 松下治、美間健彦、山本由弥子、鈴木智典、横田憲二
  • Organizer: 第87回日本細菌学会
  • Place of Presentation: 東京都江戸川区船堀
  • Year and Date: 20140326-28
• [Presentation] Structural comparison od collagen- binding domains derived from Clostridium histolyticum collagenases (2013)
  • Author(s): 松下治、美間健彦、山本由弥子、鈴木智典、横田憲二
  • Organizer: 第86回日本細菌学会
  • Place of Presentation: 千葉県千葉市
  • Year and Date: 20130318-20
• [Presentation] ガス壊疽菌群コラゲナーゼの基質認識機構の解明と臨床応用 (2012)
  • Author(s): 松下治、美間健彦、鈴木智典、山本由弥子、横田憲治、小出隆規、安達栄治郎、玉井栄治、宮田茂、南純三朗、岡部昭延
  • Organizer: 第65回日本細菌学会中国・四国支部総会
  • Place of Presentation: 徳島県徳島市
  • Year and Date: 20121020-21
• [Presentation] 細菌性コラゲナーゼの基質認識と臨床応用 (2012)
  • Author(s): 松下治
  • Organizer: 第三回愛媛微生物学ネットワークフォーラム
  • Place of Presentation: 愛媛県松山市
  • Year and Date: 2012-11-10
  • Invited
• [Presentation] Bacterial collagen-binding domains - Molecular basics and clinical applications (2012)
  • Author(s): Osamu Matsushita, Takehiko Mima, Eijiro Adachi, Joshua Sakon, Nozomu Nishi, Takenori Miyashita, NozomuMori, JoeInoue, Masakazu Hattori, Minekatsu Akimoto, Akira Takeda, Eiju Uchinuma
  • Organizer: 第85回日本細菌学会総会
  • Place of Presentation: 長崎県長崎市
  • Year and Date: 2012-03-27
• [Book] ハリソン内科学第4版(分担和訳) (2013)
  • Author(s): 福井次矢,黒川清監修
  • Total Pages: 3,120
  • Publisher: メディカルサイエンスインターナショナル
• [Book] シンプル微生物学(分担執筆) (2011)
  • Author(s): 東匡伸,小熊惠二,堀田博編集
  • Total Pages: 436
  • Publisher: 南江堂
• [Remarks]
  • URL: http://www.okayama-u.ac.jp/user/saikin/
• [Patent(Industrial Property Rights)] Fusion protein of collagen-binding domain and parathyroid hormone (2013)
  • Inventor(s): O.Matsushita, R. C. Gensure, and J. Sakon
  • Industrial Property Rights Holder: The Board of Trustees of the University of Arkansas, Ochsner Clinic Foundation, National University Corporation Kagawa University
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: US 8,450,273
  • Filing Date: 2013-05-28
• [Patent(Industrial Property Rights)] 成長因子アンカーリング型骨移植材料、成長因子アンカーリング型骨移植材料の製造方法、成長因子アンカーリング型骨移植材料製造用キット、および骨形成方法 (2012)
  • Inventor(s): 内田健太郎、成瀬康治、高相晶士、美間健彦、松下治、他2名
  • Industrial Property Rights Holder: 国立大学法人香川大学、学校法人北里研究所
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2012/057829
  • Filing Date: 2012-03-26
• [Patent(Industrial Property Rights)] 成長因子アンカーリング型骨移植材料 (2011)
  • Inventor(s): 内田健太郎、成瀬康治、高相晶士、美間健彦、松下治、原口高志、西望
  • Industrial Property Rights Holder: 学校法人北里研究所、国立大学法人香川大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特願2011-108650
  • Filing Date: 2011-05-13
  • Overseas
• [Patent(Industrial Property Rights)] 上皮層含有組織の再生材および再生評価方法 (2011)
  • Inventor(s): 宮下武憲、森望、西望、安達栄治郎、松下治、服部雅一、他2名
  • Industrial Property Rights Holder: 国立大学法人香川大学、学校法人北里研究所
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT/JP2011/060952
  • Filing Date: 2011-05-12