生体適合性ポリマーによる高潤滑型関節機能改善剤の基礎的検討

2009 Fiscal Year Annual Research Report

• Project/Area Number: 19390388
• Research Institution: The University of Tokyo
• Principal Investigator: 茂呂 徹 The University of Tokyo, 医学部附属病院, 特任准教授 (20302698)
• Co-Investigator(Kenkyū-buntansha): 高取 吉雄 東京大学, 医学部附属病院, 特任教授 (40179461) ; 石原 一彦 東京大学, 大学院・工学系研究科, 教授 (90193341) ; 川口 浩 東京大学, 医学部附属病院, 准教授 (40282660) ; 金野 智弘 東京大学, 大学院・工学系研究科, 助教 (80371706) ; 苅田 達郎 東京大学, 医学部附属病院, 講師 (80359611)
• Keywords: 医療・福祉 / 生体材料 / ナノバイオ / バイオテクノロジー / トランスレーショナルリサーチ

Research Abstract

本研究の目的は、ヒアルロン酸・MPCポリマーを用いた関節機能改善剤を実用化するための基礎検討を完成させることである。今年度は、以下の検討を行った。
1.分子構造の規格化
昨年度までに得られた知見に基づき水溶性MPCポリマーの分子組成、分子量を制御パラメーターとし、その分子構造の規格化を行った。また、体外排泄時の評価に使用する蛍光性モノマーを組み込んだポリマーを合成した。これらの検討の結果、MPCポリマーの組成、分子量を制御することに成功した。さらに体外排泄の閾値とされる分子量のポリマーから形成する関節機能改善剤の創製に成功し、ラット静脈内投与後に体外排泄性を確認することができた。
2.摩擦試験による混合比率についての検討
昨年度までの検討に基づき、MPCポリマー溶液、ヒアルロン酸溶液、MPC-ヒアルロン酸共重合体水溶液それぞれについて、至適な水溶液濃度を検討した。さらにこれらの結果から条件の絞り込みを行い、Pin-on-flat型の摩擦試験に用い、経時的な静摩擦係数、動摩擦係数の変化から至適な混合比率を計測した。さらに各混合溶液中を回収して分子量計測を行い、分子量の経時的な変化と、関節保護・摩擦抑制効果の維持・増強機構の関連についても検討した。
3.マウス変形性関節症(OA)モデルを用いた関節機能改善効果の検討
昨年度までに確立したマウス変形性関節症(OA)のモデルを用い、上記1、2で至適条件を検討した関節機能改善剤の効果を検討した。マウス膝関節の靭帯の切離と、半月板切除を組み合わせて重傷度の異なる変形性膝関節症を再現し、各々に関節機能改善剤を投与した。画像評価、組織学的検討等により、関節機能改善剤としての有効性の確認を行った。
以上の結果は、生体適合性ポリマーによる高潤滑型関節機能改善剤実用化へ向けた基礎検討を推進するための確信を得るに十分な結果であった。

Research Products

• [Journal Article] Selection of highly osteogenic and chondrogenic cells from bone marrow stromal cells in biocompatible polymer-coated plates. (2010)
  • Author(s): Liu G, Iwata K, Ogasawara T, Watanabe J, Fukazawa K, Ishihara K, Asawa Y, Fujihara Y, Chung UI, Moro T, Takatori Y, Takato T, Nakamura K, Kawaguchi H, Hoshi K
  • Journal Title: J Biomed Mater Res A (in press)
  • Peer Reviewed
• [Journal Article] Cohort profile : Research on Osteoarthritis/Osteoporosis Against Disability study. (2010)
  • Author(s): Yoshimura N, Muraki S, Oka H, Kawaguchi H, Nakamura K, Akune T
  • Journal Title: Int J Epidemiol (in press)
  • Peer Reviewed
• [Journal Article] Aktl in chondrocytes controls cartilage calcification during endochondral ossification under physiological and pathological conditions. (2010)
  • Author(s): Fukai A, Kawamura N, Saito T, Oshima Y, Ikeda T, Kugimiya F, Higashikawa H, Yano F, Ogata N, Nakamura K, Chung UI, Kawaguchi H
  • Journal Title: Arthritis Rheum (in press)
  • Peer Reviewed
• [Journal Article] Self-initiated surface grafting with poly(2-methacryloyloxyethyl phosphorylcholine)on poly(ether-ether-ketone). (2010)
  • Author(s): Kyomoto M, Moro T, Takatori Y, Kawaguchi H, Nakamura K, Ishihara K
  • Journal Title: Biomaterials (in press)
  • Peer Reviewed
• [Journal Article] Smart controlled preparation of multilayered hydrogel for releasing bioactive molecules. (2009)
  • Author(s): Choi J, Konno T, Takai M, Ishihara K
  • Journal Title: Current Applied Physics 9(4) Pages: 259-262
  • Peer Reviewed
• [Journal Article] Super-hydrophilic silicone hydrogels composed of interpenetrating polymer networks with phospholipid polymer. (2009)
  • Author(s): Shimizu T, Konno T, Takai M, Ishihara K
  • Journal Title: Trans. Mater. Res. Soc 34(2) Pages: 193-196
  • Peer Reviewed
• [Journal Article] Controlled drug release from multilayered phospholipid polymer hydrogel on titanium alloy surface (2009)
  • Author(s): Choi J, Konno T, Takai M, Ishihara K
  • Journal Title: Biomaterials 30(28) Pages: 5201-5208
  • Peer Reviewed
• [Journal Article] Surface modification by 2-methacryloyloxyethyl phosphorylcholine coupled to a photolabile linker for cell micropatterning. (2009)
  • Author(s): Jang K, Sato K, Konno K, Ishihara K, Kitamori T
  • Journal Title: Biomaterials 30(7) Pages: 1413-1420
  • Peer Reviewed
• [Journal Article] C/EBPβ promotes transition from proliferation to hypertrophic differentiation of chn ofondrocytes through transactivatiop57^<kip2>. (2009)
  • Author(s): Hirata M, Kugimiya F, Fukai A, Ohba S, Kawamura N, Ogasa wara T, Kawasaki Y, Saito T, Yano F, Ikeda T, Nakamura K, Chung UI, Kawaguchi H
  • Journal Title: PLOS ONE 4 Pages: 4543e
  • Peer Reviewed
• [Journal Article] Association of occupational activity with radiographic knee osteoarthritis and lumbar spondylosis in elderly patients of population-based cohorts : A large-scale population-based study. (2009)
  • Author(s): Muraki S, Akune T, Oka H, Mabuchi A, En-yo Y, Yoshida M, Saika A, Nakamura K, Kawaguchi H, Yoshimura N
  • Journal Title: Arthritis Rheum 61 Pages: 779-786
  • Peer Reviewed
• [Journal Article] Effects of mobility/immobility of surface modification by 2-methacryloyloxyethyl phosphorylcholine polymer on the durability of polyethylene for artificial joints. (2009)
  • Author(s): Kyomoto M, Moro T, Miyaji F, Hashimoto M, Kawaguchi H, Takatori Y, Nakamura K, Ishihara K
  • Journal Title: J Biomed Mater Res A 90 Pages: 362-371
  • Peer Reviewed
• [Journal Article] Prevalence of knee osteoarthritis, lumbar spondylosis, and osteoporosis in Japanese men and women : the research on osteoarthritis/osteoporosis against disability study. (2009)
  • Author(s): Yoshimura N, Muraki S, Oka H, Mabuchi A, En-Yo Y, Yoshida M, Saika A, Yoshida H, Suzuki T, Yamamoto S, Ishibashi H, Kawaguchi H, Nakamura K, Akune T
  • Journal Title: J Bone Miner Metab 27 Pages: 628-620
  • Peer Reviewed
• [Journal Article] Prevalence of radiographic knee osteoarthritis and its association with knee pain in the elderly of Japanese population-based cohorts : The ROAD study. (2009)
  • Author(s): Muraki S, Oka H, Akune T, Mabuchi A, En-yo Y, Yoshida M, Saika A, Suzuki T, Yoshida H, Ishibashi H, Yamamoto S, Nakamura K, Kawaguchi H, Yoshimura N
  • Journal Title: Osteoarthritis Cartilage 17 Pages: 1143-1137
  • Peer Reviewed
• [Journal Article] Superlubricious surface mimicking articular cartilage by grafting poly(2-methacryloyloxyethyl phosphorylcholine)on orthopaedic metal bearings. (2009)
  • Author(s): Kyomoto M, Moro T, Iwasaki Y, Miyaji F, Kawaguchi H, Takatori Y, Nakamura K, Ishihara K
  • Journal Title: J Biomed Mater Res A 91 Pages: 741-730
  • Peer Reviewed
• [Journal Article] Regulation of osteoarthritis development by Wnt-β-catenin signaling through the endochondral ossification process. (2009)
  • Author(s): Kawaguchi H
  • Journal Title: J Bone Miner Res 24 Pages: 8-11
  • Peer Reviewed
• [Journal Article] Osteovisual「変形性関節症における軟骨破壊のメカニズム」 (2009)
  • Author(s): 川口浩
  • Journal Title: Arthritis 16 Pages: 149-153
  • Peer Reviewed
• [Journal Article] 遺伝子変異マウスによる変形性関節症の病態解明へのアプローチ. (2009)
  • Author(s): 川口浩
  • Journal Title: The Bone 23 Pages: 35-40
  • Peer Reviewed
• [Journal Article] 変形性関節症:研究・診療の現状と問題点. (2009)
  • Author(s): 川口浩
  • Journal Title: 日本老年病学会雑誌 46 Pages: 121-127
  • Peer Reviewed
• [Journal Article] 変形性関節症に対する分子標的治療の展望 (2009)
  • Author(s): 川口浩
  • Journal Title: CLINICAL CALCIUM 19 Pages: 1608-1614
  • Peer Reviewed
• [Presentation] 細胞親和性リン脂質ポリマーハイドロゲルによる細胞機能の保持 (2009)
  • Author(s): 福栄晟、金野智浩、石原一彦
  • Organizer: 第19回日本MRSシンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 20091207-20091209
• [Presentation] 可逆形成-自発解離型MPCポリマーハイドロゲルによる細胞の長期固定化と細胞周期の同調 (2009)
  • Author(s): 福栄晟、金野智浩、石原一彦
  • Organizer: 第31回日本バイオマテリアル学会
  • Place of Presentation: 京都
  • Year and Date: 20091116-20091117
• [Presentation] Preparation of poly(2-methacryloyloxyethyl phosphorylcholine)/hydroxyapatite hybrid matrix (2009)
  • Author(s): Toyomoto Y, Matsuno R, Konnno T, Takai M, Ishihara K
  • Organizer: JST-CREST international symposium
  • Place of Presentation: Tokyo
  • Year and Date: 20091109-20091110
• [Presentation] Functional control of cells on phospholipid polymer surface with phenylboronic acid moiety (2009)
  • Author(s): Saito A, Konno T, Ikake H, Kurita K, Ishihara K
  • Organizer: International Symposium on Nanobio-Interfaces Related to Molecular Mobility
  • Place of Presentation: Tokyo
  • Year and Date: 20091109-20091110
• [Presentation] Preparation of poly(2-methacryloyloxyethyl phosphorylcholine)/hydroxyapatite hybrid matrix (2009)
  • Author(s): Toyomoto Y, Matsuno R, Konnno T, Takai M, Ishihara K
  • Organizer: JST-CREST international symposium
  • Place of Presentation: 東京
  • Year and Date: 20091109-20091110
• [Presentation] Functional control of cells on phospholipid polymer surface with phenylboronic acid moiety (2009)
  • Author(s): Saito A, Konno T, Ikake H, Kurita K, Ishihara K
  • Organizer: International Symposium on Nanobio-Interfaces Related to Molecular Mobility
  • Place of Presentation: 東京
  • Year and Date: 20091109-20091110
• [Presentation] 変形性関節症の治療標的分子へのアプローチ (2009)
  • Author(s): 川口浩
  • Organizer: 第82回日本生化学(シンポジウム「運動器形成・再生のための分子基盤」
  • Place of Presentation: 兵庫
  • Year and Date: 20091021-20091024
• [Presentation] 自発形成-解離性リン脂質ポリマーハイドロゲルによる幹細胞保持と機能評価 (2009)
  • Author(s): 金野智浩、石原一彦
  • Organizer: 第58回高分子討論会
  • Place of Presentation: 熊本
  • Year and Date: 20090916-20090918
• [Presentation] Notch/RBPJk/Hesl signaling controls terminal differentiation of chondrocytes during endochondral ossification. (2009)
  • Author(s): Hikata T, Saito T, Takaishi H, Akiyama H, Nakamura T, Yamaguchi A, Matsumoto M, Chiba K, Toyama Y, Kawaguchi H
  • Organizer: 31th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 20090911-20090915
• [Presentation] Association of knee osteoarthritis, lumbar spondylosis and osteoporosis with mild cognitive impairment : The ROAD(Research on Osteoarthritis/osteoporosis Against Disability)study. (2009)
  • Author(s): Yoshimura N, Muraki S, Oka H, Kawaguchi H, Nakamura K, Akune T
  • Organizer: 31th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 20090911-20090915
• [Presentation] Comprehensive control of endochondral ossification by HIF-2α during skeletal growth and osteoarthritis progression. (2009)
  • Author(s): Saito T, Fukai A, Ikeda T, Yano F, Hirata M, Kan A, Nakamura K, Chung UI, Kawaguchi H
  • Organizer: 31th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 20090911-20090915
• [Presentation] A novel thienoindazole-derivative small compound induces chondrogenic differentiation without promoting hypertrophy through Runxl. (2009)
  • Author(s): Yano F, Ikeda T, Saito T, Ogata N, Hojo H, Kimura A, Takeda S, Takato T, Nakamura K, Kawaguchi H, Chung UI
  • Organizer: 31th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 20090911-20090915
• [Presentation] Regulator of G protein signaling(RGS)-2 enhances bone anabolic action of PTH through inhibition of Gαq/PKC pathway in osteoblasts. (2009)
  • Author(s): Ogata N, Yano F, Chikazu D, Chung UI, Nakamura K, Kawaguchi H
  • Organizer: 31th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 20090911-20090915
• [Presentation] Health-related quality of life in subjects with vertebral fracture, knee osteoarthritis, lumbar spondylosis and other chronic diseases as well as low back pain and knee pain in a population-based cohort study in Japan : The ROAD study. (2009)
  • Author(s): Muraki S, Akune T, Oka H, Nakamura K, Kawaguchi H, Yoshimura N
  • Organizer: 31th annual meeting of the American Society for Bone and Mineral Research(ASBMR)
  • Place of Presentation: Denver, Colorado, USA
  • Year and Date: 20090911-20090915
• [Presentation] NF-kappa B family member RelA/p65, a transcription factor of Sox9, is essential for chondrogenic differentiation and skeletal growth. (2009)
  • Author(s): Itoh S, Saito T, Ushita M, Ikeda T, Yano F, Ogata N, Chung UI, Nakamura K, Kawaguchi H
  • Organizer: 2009 World Congress on Osteoarthritis(OARSI)
  • Place of Presentation: Monteral, Quebec, Canada
  • Year and Date: 20090910-20090913
• [Presentation] Distinct transcriptional control of chondrocyte hypertrophy and cartilage degeneration by C/EBP-beta and Runx2 during endochondral ossification. (2009)
  • Author(s): Hirata M, Kugimiya F, Fukai A, Saito T, Kan A, Higashikawa A, Yano F, Ikeda T, Nakamura K, Chung UI, Kawaguchi H
  • Organizer: 2009 World Congress on Osteoarthritis(OARSI)
  • Place of Presentation: Monteral, Quebec, Canada
  • Year and Date: 20090910-20090913
• [Presentation] Aktl in chondrocytes controls cartilage calcification during osteophyte foration in osteoarthritis. (2009)
  • Author(s): Fukai A, Kawamura N, Saito T, Ikeda T, Ogata N, Nakamura K, Chung UI, Kawaguchi H
  • Organizer: 2009 World Congress on Osteoarthritis(OARSI)
  • Place of Presentation: Monteral, Quebec, Canada
  • Year and Date: 20090910-20090913
• [Presentation] Automated quantification and diagnosis of the knee on plain radiographs : The ROAD study. (2009)
  • Author(s): Oka H, Akune T, Muraki S, Nakamura K, Kawaguchi H, Yoshimura N
  • Organizer: 2009 World Congress on Osteoarthritis(OARSI)
  • Place of Presentation: Monteral, Quebec, Canada
  • Year and Date: 20090910-20090913
• [Presentation] フェニルボロン酸基を有する細胞親和性リン脂質ポリマーによる可逆細胞接着表面の創製 (2009)
  • Author(s): 斉藤あや、金野智浩、伊掛浩輝、栗田公夫、石原一彦
  • Organizer: 平成21年度繊維学会年次大会
  • Place of Presentation: 東京
  • Year and Date: 20090610-20090612
• [Presentation] 細胞ナノシステムによるバイオハイブリッドナノマシン構築-ナノマシンの自己組織的組み立てに向けた細胞移動の制御- (2009)
  • Author(s): 星野隆行、金野智浩、石原一彦、森島圭祐
  • Organizer: 第81回日本リウマチ学会総会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20090525-20090526
• [Presentation] 変形性関節症の診断と治療:最近の進歩 (2009)
  • Author(s): 川口浩
  • Organizer: 第81回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20090423-20090426
• [Presentation] 変形性関節症の疫学研究の現状と問題点:ROADプロジェクト(シンポジウム:OAの病態と診断) (2009)
  • Author(s): 川口浩、阿久根徹、岡敬之、村木重之、中村耕三、吉村典子
  • Organizer: 第81回日本リウマチ学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 20090423-20090426
• [Presentation] Cartilage degeneration during osteoarthritis progression. (2009)
  • Author(s): Kawaguchi H
  • Organizer: 第18回国際リウマチシンポジウム
  • Place of Presentation: 東京
  • Year and Date: 20090423-20090426
• [Presentation] ポリマーブラシ表面がタンパク質吸着に与える因子の解明 (2009)
  • Author(s): 磯江晋輔、松野亮介、金野智浩、高井まどか、石原一彦
  • Organizer: 日本バイオマテリアル学会シンポジウム2009
  • Place of Presentation: 京都
  • Year and Date: 2009-11-17
• [Presentation] Molecular backgrounds of cartilage degeneration during osteoarthritis progression. (2009)
  • Author(s): Kawaguchi H
  • Organizer: The 35th Annual Meeting of the Korean Orthopaedic Research Society
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-10-14
• [Presentation] Transcriptional regulation of cartilage degeneration during osteoarthritis progression. (2009)
  • Author(s): Kawaguchi H
  • Organizer: The 2nd International Cartilage and Osteoarthritis Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2009-10-10
• [Presentation] Control of ES Cell Functions in Biocompatible Reversible Hydrogel System (2009)
  • Author(s): Ishihara K, Konno T
  • Organizer: 2009 Asia Conference for Biomaterials & Stem Cell Techniques
  • Place of Presentation: Taiwan
  • Year and Date: 2009-09-21
• [Presentation] Novel stable fluorescence nanoparticles covered with biocompatible phospholipid polymers and specific biomolecules. (2009)
  • Author(s): Ishihara K, Goto Y, Matsuno R, Konno T, Takai M
  • Organizer: Controlled Release Society Annual Meeting
  • Place of Presentation: Copenhagen
  • Year and Date: 2009-07-21
• [Presentation] Antithrombogenic Polymer Alloy with Well-defined Block-type Phospholipid Polymer and Segmented Polyurethane for Cardiovascular Medical Devices. (2009)
  • Author(s): Ishihara K, Matsuno R, Konno T, Takai M, Asanuma Y
  • Organizer: 2nd Asian Congress of Biomaterials
  • Place of Presentation: Singapore
  • Year and Date: 2009-06-26