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Local delivery of small interfering RNA using biodegradable polymer application to enhance bone morphogenetic protein-induced bone formation

Research Project

Project/Area Number 21791408
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionOsaka City University

Principal Investigator

SUZUKI Akinobu  Osaka City University, 大学院・医学研究科, 病院講師 (00445016)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsポリマー / 骨形成蛋白(Bone morphogenetic protein;BMP) / Noggin / 骨再生 / siRNA / rhBMP-2
Research Abstract

In this study, we investigated the efficacy of a biodegradable hydrogel, poly-D,L-lactic acid-p-dioxanone-polyethylene glycol block co-polymer (PLA-DX-PEG), as a siRNA carrier. PLA-DX-PEG pellets with or without fluorescein-labeled dsRNA were implanted into mouse dosal muscle pouches. The cellular uptake of dsRNA surround the polymer was confirmed by fluorescent microscopy. The fluorescence intensity was dose dependent of the dsRNA, and exhibited a time-dependent decrease. To investigate its biological efficiency, noggin (antagonoist to BMPs) gene silencing with siRNA (siRNA/Noggin) was examined by the amount of suppression of BMP-2-induced noggin expression and the level of performance of BMP, indicated by ectopic bone formation. Noggin gene expression induced by BMP-2 was suppressed by addition of siRNA /Noggin to the implant, and the ectopic-bone formation induced by implants with both BMP-2 and siRNA/Noggin was significantly greater than those induced by implants with BMP-2 alone. These results indicate the efficacy of local delivery of siRNAs by PLA-DX-PEG polymer, which intensified bone-inducing effects of BMP and promoted new bone formation by suppressing gene expression of Noggin.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (43 results)

All 2011 2010 2009

All Journal Article (20 results) (of which Peer Reviewed: 15 results) Presentation (23 results)

  • [Journal Article] Cellularity and Cartilage Matrix Increased in Hypertrophied Ligamentum Flavum : Histopathological Analysis Focusing on the Mechanical Stress and Bone Morphogenetic Protein Signaling.2011

    • Author(s)
      Shafaq N, Suzuki A, Terai H, Wakitani S, Nakamura H.
    • Journal Title

      J Spinal Disord Tech. (in press)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Characteristic radiographic or magnetic resonance images of fresh osteoporotic vertebral fractures predicting potential risk for non-union : a prospective multicenter study.2011

    • Author(s)
      Tsujio T, Nakamura H, Terai H, Hoshino M, Namikawa T, Matsumura A, Kato M, Suzuki A, Takayama K, Fukushima W, Kondo K, Hirota Y, Takaoka K.
    • Journal Title

      Spine. (in press)

    • NAID

      10030715746

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differentiating Benign Notochordal Cell Tumors From Chordomas : Radiographic Features on MRI, CT, and Tomography.2011

    • Author(s)
      Nishiguchi T, Mochizuki K, Ohsawa M, Inoue T, Kageyama K, Suzuki A, Takami T, Miki Y.
    • Journal Title

      AJR Am J Roentgenol. 196(3)

      Pages: 644-650

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differentiating Benign Notochordal Cell Tumors From Chordomas : Radiographic Features on MRI, CT, and Tomography.2011

    • Author(s)
      Nishiguchi T, Mochizuki K, Ohsawa M, Inoue T, Kageyama K, Suzuki A, Takami T, Miki Y.
    • Journal Title

      Am J Roentgenol

      Volume: 196(3) Pages: 644-50

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk Factor Analysis for Motor Deficit and Delayed Recovery Associated With L4/5 Lumbar Disc Herniation2011

    • Author(s)
      Suzuki A, Matsumura A, Konishi S, Terai H, Tsujio T, Dozono S, Nakamura H
    • Journal Title

      J Spinal Disord Tech

      Volume: 24(1) Pages: 1-5

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 骨折治癒・骨再生における神経系の関与2010

    • Author(s)
      鈴木亨暢, 上村卓也, 中村博亮
    • Journal Title

      Clinical Calcium 20(12)

      Pages: 1820-1827

    • Related Report
      2010 Final Research Report
  • [Journal Article] Vertebroplastyとkyphoplasty2010

    • Author(s)
      鈴木亨暢, 中村博亮
    • Journal Title

      骨粗鬆症治療 9(3)

      Pages: 269-272

    • Related Report
      2010 Final Research Report
  • [Journal Article] The influence of approach side on facet preservation in microscopic bilateral decompression via a unilateral approach for degenerative lumbar scoliosis.2010

    • Author(s)
      Matsumura A, Namikawa T, Terai H, Tsujio T, Suzuki A, Dozono S, Yasuda H, Nakamura H.
    • Journal Title

      J Neurosurg Spine. 13(6)

      Pages: 758-765

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Risk Factor Analysis for Motor Deficit and Delayed Recovery Associated With L4/5 Lumbar Disc Herniation.2010

    • Author(s)
      Suzuki A, Matsumura A, Konishi S, Terai H, Tsujio T, Dozono S, Nakamura H.
    • Journal Title

      J Spinal Disord Tech. (in press)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Clinical outcomes of microscopic decompression for degenerative lumbar foraminal stenosis : a comparison between patients with and without degenerative lumbar scoliosis.2010

    • Author(s)
      Yamada K, Matsuda H, Nabeta M, Habunaga H, Suzuki A, Nakamura H.
    • Journal Title

      Eur Spine J. (in press)

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The influence of approach side on facet preservation in microscopic bilateral decompression via a unilateral approach for degenerative lumbar scoliosis.2010

    • Author(s)
      Matsumura A, Namikawa T, Terai H, Tsujio T, Suzuki A, Dozono S, Yasuda H, Nakamura H.
    • Journal Title

      J Neurosurg Spine.

      Volume: 13(6) Pages: 758-65

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vertebroplastyとkyphoplasty2010

    • Author(s)
      鈴木亨暢, 中村博亮
    • Journal Title

      骨粗鬆症治療

      Volume: 9(3) Pages: 269-272

    • Related Report
      2010 Annual Research Report
  • [Journal Article] 骨折治癒・骨再生における神経系の関与2010

    • Author(s)
      鈴木亨暢, 上村卓也, 中村博亮
    • Journal Title

      Clinical Calcium

      Volume: 20(10) Pages: 1820-27

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Induction of pancreatitis-associated protein (PAP) family members in neurons following traumatic brain injury.2009

    • Author(s)
      Ampo KI, Suzuki A, Konishi H, Kiyama H.
    • Journal Title

      J Neurotrauma. 26(10)

      Pages: 1683-1693

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recovery process following cervical laminoplasty in patients with cervical compression myelopathy : prospective cohort study.2009

    • Author(s)
      Suzuki A, Misawa H, Simogata M, Tsutsumimoto T, Takaoka K, Nakamura H.
    • Journal Title

      Spine. 34(26)

      Pages: 2874-2879

    • NAID

      10027250907

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] RNA interference for noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro.2009

    • Author(s)
      Takayama K, Suzuki A, Manaka T, Taguchi S, Hashimoto Y, Imai Y, Wakitani S, Takaoka K.
    • Journal Title

      J Bone Miner Metab. 27(4)

      Pages: 402-411

    • NAID

      10027204830

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Over-expression of pancreatic pituitary adenylate cyclase-activating polypeptide (PACAP) aggravates cerulein-induced acute pancreatitis in mice.2009

    • Author(s)
      Hamagami K, Sakurai Y, Shintani N, Higuchi N, Ikeda K, Hashimoto H, Suzuki A, Kiyama H, Baba A.
    • Journal Title

      J Pharmacol Sci. 110(4)

      Pages: 451-458

    • NAID

      10025738220

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Factors affecting neurological deficits and intractable back pain in patients with insufficient bone union following osteoporotic vertebral fracture.2009

    • Author(s)
      Hoshino M, Nakamura H, Terai H, Tsujio T, Nabeta M, Namikawa T, Matsumura A, Suzuki A, Takayama K, Takaoka K.
    • Journal Title

      Eur Spine J. 18(9)

      Pages: 1279-1286

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Recovery process following cervical laminoplasty in patients with cervical compression myelopathy: prospective cohort study.2009

    • Author(s)
      Suzuki A, Misawa H, Simogata M, Tsutsumimoto T, Takaoka K, Nakamura H.
    • Journal Title

      Spine. 34(26)

      Pages: 2874-2879

    • NAID

      10027250907

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] RNA interference for noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro.2009

    • Author(s)
      高山和士、鈴木亨暢
    • Journal Title

      Journal of bone and mineral metabolism 27

      Pages: 402-411

    • NAID

      10027204830

    • Related Report
      2009 Annual Research Report
  • [Presentation] Clinical outcomes of microscopic decompression for degenerative lumbar foraminal stenosis : a comparison between patients with and without degenerative lumbar scoliosis.2011

    • Author(s)
      Suzuki A, Yamada K, Matsuda H, Nabeta M, Habunaga H, Nakamura H.
    • Organizer
      2011 Global Spine Congress
    • Place of Presentation
      Spain
    • Year and Date
      2011-03-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Clinical outcomes of microscopic decompression for degenerative lumbar foraminal stenosis : a comparison between patients with and without degenerative lumbar scoliosis.2011

    • Author(s)
      Akinobu Suzuki, Kentaro Yamada, Hideki Matsuda, Masaharu Nabeta, Hiroshi Habunaga, Hiroaki Nakamura.
    • Organizer
      2011 Global Spine Congress
    • Place of Presentation
      スペイン バルセロナ
    • Year and Date
      2011-03-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Endoscopic Vertebroplasty without Instrumentation for Insufficient Bone Union with Neurological Deficit following Osteoporotic Vertebral Fracture.2011

    • Author(s)
      Akinobu Suzuki, Tadao Tsujio, Masatoshi Hoshino, Hidetomi Terai, Hiromitsu Toyoda, Hiroaki Nakamura.
    • Organizer
      2011 Global Spine Congress
    • Place of Presentation
      スペイン バルセロナ
    • Year and Date
      2011-03-23
    • Related Report
      2010 Final Research Report
  • [Presentation] Endoscopic Vertebroplasty without Instrumentation for Insufficient Bone Union with Neurological Deficit following Osteoporotic Vertebral Fracture2011

    • Author(s)
      Suzuki A, Tsujio T, Hoshino M, Terai H, Toyoda H, Nakamura H
    • Organizer
      2011 Global Spine Congress
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2011-03-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] 腰椎変性側彎症患者における傍脊柱筋変性に関する検討2010

    • Author(s)
      鈴木亨暢, Shafaq Najibullah, 松村昭, 寺井秀富, 安田宏之, 中村博亮
    • Organizer
      第116回中部日本整形外科災害外科学会
    • Place of Presentation
      大阪府大阪市
    • Year and Date
      2010-10-08
    • Related Report
      2010 Final Research Report
  • [Presentation] 腰椎変性側彎症患者における傍脊柱筋変性に関する検討2010

    • Author(s)
      鈴木亨暢, Shafaq Najibullah, 松村昭, 寺井秀富, 安田宏之, 中村博亮
    • Organizer
      中部日本整形外科災害外科学会
    • Place of Presentation
      ザ・リッツカールトン大阪、大阪
    • Year and Date
      2010-10-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経障害を合併した骨粗鬆症性椎体骨折後偽関節に対する内視鏡下椎体形成術の治療成績2010

    • Author(s)
      鈴木亨暢, 辻尾唯雄, 星野雅俊, 寺井秀富, 豊田宏光, 中村博亮
    • Organizer
      第6回椎体形成術研究会
    • Place of Presentation
      京都府京都市
    • Year and Date
      2010-08-28
    • Related Report
      2010 Final Research Report
  • [Presentation] 遅神経障害を合併した骨粗鬆症性椎体骨折後偽関節に対する内視鏡下椎体形成術の治療成績2010

    • Author(s)
      鈴木亨暢, 辻尾唯雄, 星野雅俊, 寺井秀富, 豊田宏光, 中村博亮
    • Organizer
      椎体形成術研究会
    • Place of Presentation
      メルパルク京都、京都
    • Year and Date
      2010-08-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経障害を合併した骨粗鬆症性椎体骨折後偽関節に対する内視鏡下椎体形成術の治療成績2010

    • Author(s)
      鈴木亨暢, 辻尾唯雄, 星野雅俊, 寺井秀富, 豊田宏光, 中村博亮
    • Organizer
      第83回日本整形外科学会
    • Place of Presentation
      東京都
    • Year and Date
      2010-05-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 遅神経障害を合併した骨粗鬆症性椎体骨折後偽関節に対する内視鏡下椎体形成術の治療成績2010

    • Author(s)
      鈴木亨暢, 辻尾唯雄, 星野雅俊, 寺井秀富, 豊田宏光, 中村博亮
    • Organizer
      日本整形外科学会
    • Place of Presentation
      東京国際フォーラム、東京
    • Year and Date
      2010-05-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] 遅発性神経麻痺を呈した骨粗鬆症性椎体骨折後偽関節に対する内視鏡下椎体形成術単独の治療成績2010

    • Author(s)
      鈴木亨暢, 辻尾唯雄, 星野雅俊, 寺井秀富, 豊田宏光, 松本富哉, 中村博亮
    • Organizer
      第39回日本脊椎脊髄病学会
    • Place of Presentation
      高知県、高知市
    • Year and Date
      2010-04-23
    • Related Report
      2010 Final Research Report
  • [Presentation] 遅発性神経麻痺を呈した骨粗鬆症性椎体骨折後偽関節に対する内視鏡下椎体形成術単独の治療成績2010

    • Author(s)
      鈴木亨暢, 辻尾唯雄, 星野雅俊, 寺井秀富, 豊田宏光, 松本富哉, 中村博亮
    • Organizer
      日本脊椎脊髄病学会
    • Place of Presentation
      高知県立県民文化ホール、高知
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Endoscopic Vertebroplasty without Instrumentation for Insufficient Bone Union with Neurological Deficit following Osteoporotic Vertebral Fracture.2010

    • Author(s)
      Akinobu Suzuki, Tadao Tsujio, Masatoshi Hoshino, Hidetomi Terai, Hiromitsu Toyoda, Hiroaki Nakamura.
    • Organizer
      2010 International society for study of the lumbar spine
    • Place of Presentation
      ニュージーランド、オークランド
    • Year and Date
      2010-04-13
    • Related Report
      2010 Final Research Report
  • [Presentation] Histopathological Analysis of Hypertrophic Ligamentum Flavum in Degenerative Lumber Canal Stenosis : Focus on the Expression of BMP receptor.2010

    • Author(s)
      Najibullah Shafaq, Akinobu Suzuki, Hidetomi Terai, Hiroaki Nakamura, Kunio Takaoka.
    • Organizer
      2010 International society for study of the
    • Year and Date
      2010-04-13
    • Related Report
      2010 Final Research Report
  • [Presentation] Endoscopic Vertebroplasty without Instrumentation for Insufficient Bone Union with Neurological Deficit following Osteoporotic Vertebral Fracture2010

    • Author(s)
      Suzuki A, Tsujio T, Hoshino M, Terai H, Toyoda H, Nakamura H
    • Organizer
      2010 International society for study of the lumbar spine
    • Place of Presentation
      Auckland, Newzealand
    • Year and Date
      2010-04-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経障害を合併した骨粗鬆症性椎体骨折後偽関節に対する内視鏡下椎体形成術の治療成績2009

    • Author(s)
      鈴木亨暢、辻尾唯雄、星野雅俊、寺井秀富、豊田宏光、中村博亮
    • Organizer
      第13回日本内視鏡低侵襲脊椎外科学会
    • Place of Presentation
      兵庫県、神戸市
    • Year and Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Presentation] 生体吸収性ポリマーを用いたsiRNA導入法の開発-骨再生への応用-2009

    • Author(s)
      間中智哉、鈴木亨暢、高山和士、高岡邦夫
    • Organizer
      第24回日本整形外科学会基礎学術集会
    • Place of Presentation
      神奈川県、横浜市
    • Year and Date
      2009-11-05
    • Related Report
      2010 Final Research Report
  • [Presentation] 生体吸収性ポリマーを用いたsiRNA導入法の開発-骨再生への応用-2009

    • Author(s)
      間中智哉
    • Organizer
      日本整形外科基礎学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-11-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] 頸髄症に対する頸椎椎弓形成術前後におけるQOL評価しびれ・疼痛がQOLに与える影響2009

    • Author(s)
      鈴木亨暢, 松村昭, 寺井秀富, 高橋真治, 前野考史, 中村博亮
    • Organizer
      第114回中部日本整形外科災害外科学会
    • Place of Presentation
      兵庫県、神戸市
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] The 9th Pacific Asian Society of Minimum Invasive Spine Surgery (Osaka)2009

    • Author(s)
      Akinobu Suzuki, Tadao Tsujio, Masatoshi Hoshino, Hidetomi Terai, Hiromitsu Toyoda, Hiroaki Nakamura.
    • Organizer
      Endoscopic Vertebroplasty without Instrumentation for Insufficient Bone Union with Neurological Deficit following Osteoporotic Vertebral Fracture.
    • Year and Date
      2009-08-07
    • Related Report
      2010 Final Research Report
  • [Presentation] 頸髄症における頸椎椎弓形成術後の回復経過に関する前向き研究2009

    • Author(s)
      鈴木亨暢, 三澤弘道, 下形光彦, 堤本高宏, 高岡邦夫, 中村博亮
    • Organizer
      第82回日本整形外科学会
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2009-05-16
    • Related Report
      2010 Final Research Report
  • [Presentation] 頸髄症に対する頸椎椎弓形成術前後におけるQOL評価しびれ・疼痛がQOLに与える影響2009

    • Author(s)
      鈴木亨暢, 松村昭, 中村博亮, 寺井秀富, 豊田宏光, 伊達優子, 前野考史, 高橋真治, 高岡邦夫
    • Organizer
      第38回日本脊椎脊髄病学会
    • Place of Presentation
      兵庫県、神戸市
    • Year and Date
      2009-04-24
    • Related Report
      2010 Final Research Report
  • [Presentation] 三種の評価方法を元とした頸髄症における頸椎椎弓形成術後の回復経過の前向き研究2009

    • Author(s)
      鈴木亨暢, 三澤弘道, 下形光彦, 堤本高宏, 高岡邦夫, 中村博亮
    • Organizer
      第38回日本脊椎脊髄病学会
    • Place of Presentation
      兵庫県、神戸市
    • Year and Date
      2009-04-24
    • Related Report
      2010 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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