Multidisciplinary study on the regulation of the remodeling of the patellar tendon matrix in response to mechanical environment

• Project/Area Number: 18390406
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hokkaido University
• Principal Investigator: TOHYAMA Harukazu Hokkaido University, 大学病院, 准教授 (60301884)
• Co-Investigator(Kenkyū-buntansha): YASUDA Kazurori 北海道大学, 大学院・医学研究科, 教授 (20166507) ; ONODERA Shin 北海道大学, 大学院・医学研究科, 特任講師 (00359481) ; KONDO Eiji 北海道大学, 創成科学研究機構, 特任准教授 (60374724)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,350,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥1,950,000); Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2006: ¥8,900,000 (Direct Cost: ¥8,900,000)
• Keywords: 腱・靱帯 / バイオメカ二クス / サイトカイン / 炎症 / 力学的負荷 / 廃用 / 膝蓋腱 / 力学的特性 / 生体医工学 / 除負荷 / IL-1β / バイオメカニクス / TGF-β

Research Abstract

廃用がもたらす除負荷は腱組織の力学特性を低下させることが知られているが、この機序や制御に関しては不明であった。本研究ではin vivo動物モデルを用い、除負荷が膝蓋腱細胞におけるIL-1β発現を亢進させ、IL-1抑止は除負荷膝蓋腱の力学特性を改善させることを明らかにし、廃用による腱組織の力学的劣化には炎症性サイトカインが重要な役割を担い、本サイトカイン制御により廃用がもたらす腱の力学的劣化を抑止する可能性を示した。

Research Products

• [Journal Article] Active immunization against macrophage migration inhibitory factor using a novel DNA vaccine prevents ovariectomy-induced (2008)
  • Author(s): Onodera S, Oshima S, Nishihira J, Yasuda K, Tohyama H, Irie K, Koyama Y.
  • Journal Title: bone loss in mice. Vaccine 26(6) Pages: 829-36
  • Peer Reviewed
• [Journal Article] Local administration of interleukin-1 receptor antagonist inhibits deterioration of mechanical properties of the stress-shielded patellar tendon (2008)
  • Author(s): Miyatake S, Tohyama H, Kondo E, Katsura T, Onodera S, Yasuda K
  • Journal Title: J Biomech 41(4) Pages: 884-9
  • Peer Reviewed
• [Journal Article] Ex vivo supplementation of TGF-beta1 enhances the fibrous tissue regeneration effect of synovium-derived fibroblast transplantation in a tendon defect a biomechanical study (2008)
  • Author(s): Okamoto S, Tohyama H, Kondo E, Anaguchi Y, Onodera S, Hayashi K, Yasuda K.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 16(3) Pages: 333-9
  • Peer Reviewed
• [Journal Article] Simultaneous anterior and posterior cruciate ligament reconstruction in chronic knee instabilities surgical concepts and clinical outcome. (2008)
  • Author(s): Hayashi R, Kitamura N, Kondo E, Anaguchi Y, Tohyama H, Yasuda K.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 16(8) Pages: 763-9
  • Peer Reviewed
• [Journal Article] A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis (2008)
  • Author(s): Tohyama S, Onodera S, Tohyama H, Yasuda K, Nishihira J, Mizue Y, Hamasaka A, Abe R, Koyama Y.
  • Journal Title: Gene Ther 15(23) Pages: 1513-22
  • Peer Reviewed
• [Journal Article] In vivo local administration of osteogenic protein-1 increases structural properties of the overstretched anterior cruciate ligament with partial midsubstance laceration a biomechanical study in rabbits (2008)
  • Author(s): Hayashi R, Kondo E, Tohyama H, Saito T, Yasuda K.
  • Journal Title: J Bone Joint Surg Br. 90(10) Pages: 1392-400
  • Peer Reviewed
• [Journal Article] In vivo local administration of osteogenic protein-1 increases structural properties of the overstretched anterior cruciate ligament with partial midsubstance laceration : a biomechanical study in rabbits (2008)
  • Author(s): Hayashi R
  • Journal Title: J Bone Joint Surg Br. 90(10) Pages: 1392-400
  • Peer Reviewed
• [Journal Article] A novel DNA vaccine-targeting macrophage migration inhibitory factor improves the survival of mice with sepsis (2008)
  • Author(s): Tohyama S
  • Journal Title: Gene Ther. 15(23) Pages: 1513-22
  • Peer Reviewed
• [Journal Article] Simultaneous anterior and posterior cruciate ligament reconstruction in chronic knee instabilities : surgical concepts and clinical outcome (2008)
  • Author(s): Hayashi R
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 16(8) Pages: 763-9
  • Peer Reviewed
• [Journal Article] Active immunization against macrophage migration inhibitory factor using a novel DNA vaccine prevents ovariectomy-induced bone loss in mice (2008)
  • Author(s): Onodera S
  • Journal Title: Vaccine 26(6) Pages: 829-36
  • Peer Reviewed
• [Journal Article] Local administration of interleukin-1 receptor antagonist inhibits deterioration of mechanical properties of the stress-shielded patellar tendon (2008)
  • Author(s): Miyatake S
  • Journal Title: J Biomech 41(4) Pages: 884-9
  • Peer Reviewed
• [Journal Article] 解剖学的2重束前十字靱帯再建術の臨床成績男女間の比較 (2008)
  • Author(s): 林陸
  • Journal Title: 膝 32巻2号 Pages: 227-232
  • Peer Reviewed
• [Journal Article] 前十字靱帯(ACL)・後十字靱帯(PCL)の大腿骨側付着部の研究 (2008)
  • Author(s): 寺島尚志
  • Journal Title: 関節鏡 33巻2号 Pages: 217-222
  • Peer Reviewed
• [Journal Article] Ex vivo infiltration of fibroblasts into the tendon deteriorates the mechanical properties of tendon fascicles but not those of tendon bundles (2007)
  • Author(s): Ikema Y, Tohyama H, Yamamoto E, Kanaya F, Yasuda K.
  • Journal Title: Clin Biomech (Bristol, Avon) 22(1) Pages: 120-6
  • NAID: 120000970459
  • Peer Reviewed
• [Journal Article] The tensile properties of collagen fascicles harvested from regenerated and residual tissues in the patellar tendon after removal of the central third (2007)
  • Author(s): Maeda E, Noguchi H, Tohyama H, Yasuda K, Hayashi K.
  • Journal Title: Biomed Mater Eng 17(2) Pages: 77-85
  • NAID: 40015883948
  • Peer Reviewed
• [Journal Article] A novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in murine models of arthritis (2007)
  • Author(s): Onodera S, Ohshima S, Tohyama H, Yasuda K, Nishihira J, Iwakura Y, Matsuda I, Minami A, Koyama Y.
  • Journal Title: Arthritis Rheum 56(2) Pages: 521-30
  • NAID: 40017099467
  • Peer Reviewed
• [Journal Article] Antibody neutralization of TGF-beta enhances the deterioration of collagen fascicles in a tissue-cultured tendon matrix with ex vivo fibroblast infiltration (2007)
  • Author(s): Azuma C, Tohyama H, Nakamura H, Kanaya F, Yasuda K.
  • Journal Title: J Biomech 40(10) Pages: 2184-90
  • Peer Reviewed
• [Journal Article] Radiologic evaluation of femoral and tibial tunnels created with the transtibial tunnel technique for anatomic double-bundle anterior cruciate ligament reconstruction (2007)
  • Author(s): Kondo E, Yasuda K, Ichiyama H, Azuma C, Tohyama H.
  • Journal Title: Arthroscopy 23(8) Pages: 869-76
  • Peer Reviewed
• [Journal Article] In vivo effects of partial electrothermal shrinkage on mechanical properties of the anterior cruciate ligament in rabbits (2007)
  • Author(s): Kondo E, Yasuda K, Tohyama H.
  • Journal Title: Clin Biomech (Bristol, Avon) 22(9) Pages: 1037-44
  • NAID: 120000949894
  • Peer Reviewed
• [Journal Article] The responses of extrinsic fibroblasts infiltrating the devitalised patellar tendon to IL-1beta are different from those of normal tendon fibroblasts (2007)
  • Author(s): Tohyama H, Yasuda K, Uchida H, Nishihira J.
  • Journal Title: J Bone Joint Surg Br. 89(9) Pages: 1261-7
  • Peer Reviewed
• [Journal Article] The tensile properties of collagen fascicles harvested from regenerated and residual tissues in the patellar tendon after removal of the central third. (2007)
  • Author(s): Maeda E
  • Journal Title: Biomed Mater Eng. 17(2) Pages: 77-85
  • Peer Reviewed
• [Journal Article] A Novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in models of arthritis. (2007)
  • Author(s): Onodera S
  • Journal Title: Arthritis Rheum. 56(2) Pages: 521-30
  • Peer Reviewed
• [Journal Article] Ex vivo infiltration of fibroblasts into the tendon deteriorates the mech anical properties of tendon fascicles but not thoseof tendon bundles (2007)
  • Author(s): Ikema Y
  • Journal Title: Cliu Biomech (Bristol, Avon) 22(1) Pages: 120-6
  • Peer Reviewed
• [Journal Article] Antibody neutralization of TGF-beta enhances the deterioration of collagen fascicles in a tissue-cultured tendon matrix with ex vivo fibroblast infiltration (2007)
  • Author(s): Azuma C
  • Journal Title: J Biomech 40(10) Pages: 2184-90
  • Peer Reviewed
• [Journal Article] Radiologic evaluiation of femoral and tibial tunnels created with the transtibial tunnel technique for anatomic double-bundle anterior cruciate ligament reconstruction (2007)
  • Author(s): Kondo E
  • Journal Title: Arthroscopy 23(8) Pages: 869-76
  • Peer Reviewed
• [Journal Article] In vivo effects of partial electrothermal shrinkage on mechanical properties of the anterior cruciate ligament in rabbits. (2007)
  • Author(s): Kondo E.
  • Journal Title: Clin Biomech(Bristol, Avon). 22(9) Pages: 1037-44
  • NAID: 120000949894
  • Peer Reviewed
• [Journal Article] The responses of extrinsic fibroblasts infiltrating the devitalised patellar tendon to IL-1beta are different. from those of normal tendon fibroblasts (2007)
  • Author(s): Tohyama H
  • Journal Title: J Bone Joint Surg Br. 89(9) Pages: 1261-7
  • Peer Reviewed
• [Journal Article] Ex yivo infiltration of fibroblasts into the tendon deteriortes the mechanical properties of tendon fascicles but not those of tendon bundles. (2007)
  • Author(s): Ikema Y, Tohyama H, et al.
  • Journal Title: Clin Biomech (Bristol, Avon) 22(1) Pages: 120-126
• [Journal Article] A novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in murine models of arthritis. (2007)
  • Author(s): Onodera S, Ohshima S, Tohyama H, et al.
  • Journal Title: Arthritis Rheum 56(2) Pages: 521-530
  • NAID: 40017099467
• [Journal Article] Effects of Local Administration of Vascular Endothelial Growth Factor on Properties of the in Situ Frozen-Thawed Anterior Cruciate Ligament in Rabbits (2006)
  • Author(s): Ju YJ, Tohyama H, Kondo E, Yoshikawa T, Muneta T, Shinomiya K, Yasuda K.
  • Journal Title: Am J Sports Med. 6:34(1) Pages: 84-91
  • Peer Reviewed
• [Journal Article] Stabilizing effects of ankle bracing under a combination of inversion and axial compression loading (2006)
  • Author(s): Tohyama H, Yasuda K, Beynnon BD, Renstrom PA.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 14(4) Pages: 373-8
  • NAID: 120000953047
  • Peer Reviewed
• [Journal Article] Clinical evaluation of anatomic double-bundle anterior cruciate ligament reconstruction procedure using hamstring tendon grafts comparisons among 3 different procedures (2006)
  • Author(s): Yasuda K, Kondo E, Ichiyama H, Tanabe Y, Tohyama H.
  • Journal Title: Arthroscopy 22(3) Pages: 240-51
  • Peer Reviewed
• [Journal Article] Effects of administration of transforming growth factor (TGF)-beta1 and anti-TGF-beta1 antibody on the mechanical properties of the stress-shielded patellar tendon (2006)
  • Author(s): Katsura T, Tohyama H, Kondo E, Kitamura N, Yasuda K.
  • Journal Title: J Biomech 39(14) Pages: 2566-72
  • Peer Reviewed
• [Journal Article] Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction (2006)
  • Author(s): Yoshikawa T, Tohyama H, Enomoto H, Matsumoto H, Toyama Y, Yasuda K.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 14(9) Pages: 804-10
  • Peer Reviewed
• [Journal Article] Effects of local administration of vascular endothelial growth factor on mechanical characteristics of the semitendinosus tendon graft after anterior cruciate ligament reconstruction in sheep (2006)
  • Author(s): Yoshikawa T, Tohyama H, Katsura T, Kotani Y, Matsumoto H, Toyama Y, Yasuda K
  • Journal Title: Am J Sports Med 34(12) Pages: 1918-25
  • Peer Reviewed
• [Journal Article] Is the increase in type III collagen of the patellar tendon graft after ligament reconstruction really caused by "ligamentization" of the graft? (2006)
  • Author(s): Tohyama H, Uchida H, Yasuda K.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 14(12) Pages: 1270-7
  • NAID: 120000972278
  • Peer Reviewed
• [Journal Article] Transgenic mice overexpressing macrophage migration inhibitory factor (MIF) exhibit high-turnover osteoporosis (2006)
  • Author(s): Onodera S, Sasaki S, Ohshima S, Amizuka N, Li M, Udagawa N, Irie K, Nishihira J, Koyama Y, Shiraishi A, Tohyama H, Yasuda K.
  • Journal Title: Bone Miner Res 21(6) Pages: 876-85
  • Peer Reviewed
• [Journal Article] The effect of intraosseous graft length on tendon-bone healing in anterior cruciate ligament reconstruction using flexor tendon (2006)
  • Author(s): Yamazaki S, Yasuda K, Tomita F, Minami A, Tohyama H.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 14(11) Pages: 1086-93
  • NAID: 120000964243
  • Peer Reviewed
• [Journal Article] Effects of local administration of vascular endothelial growth factor on mechanical characteristics of the semitendinosus tendon graft after anterior cruciate ligament reconstruction in sheep. (2006)
  • Author(s): Yoshikawa T, Tohyama H, et al.
  • Journal Title: Am J Sports Med. 34(12) Pages: 1918-1925
• [Journal Article] The effect of intraosseous graft length on tendon-bone healing in anterior cruciate ligament reconstruction using flexor tendon. (2006)
  • Author(s): Yamazaki S, Yasuda K, Tomita F, Minami A, Tohyama H.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 14(11) Pages: 1086-1093
  • NAID: 120000964243
• [Journal Article] Is the increase in type III collagen of the patellar tendon. graft after ligament reconstruction really caused by ligamentization of the graft? (2006)
  • Author(s): Tohyama H, Yasuda K, Uchida H
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 14(12) Pages: 1270-1277
  • NAID: 120000972278
• [Journal Article] Expression of vascular endothelial growth factor and angiogenesis in patellar tendon grafts in the early phase after anterior cruciate ligament reconstruction (2006)
  • Author(s): Yoshikawa T, Tohyama H, et al.
  • Journal Title: Knee Surg Sports Traumatol Arthrosc 14(9) Pages: 804-810
• [Presentation] The relationship between open and closed kinetic chain strength of the lower limb and jumping performance in ACL-deficient subjects and ACL-reconstructed Subjects using anatomical double-bundle reconstruction (2009)
  • Author(s): Tohyama H
  • Organizer: International Symposium on Ligaments & Tendons
  • Place of Presentation: Las Vegas, NV, USA
  • Year and Date: 2009-02-21
• [Presentation] The relationship between open and closed kinetic chain strength of the lower limb and jumping performance in the anterior cruciate ligament deficient Subjects (2008)
  • Author(s): Tohyama H, Ikoma K, Ueda M, Yuri M, Chiba T, Urayama R, Hori K, Yasuda K.
  • Organizer: the XVII Congress of International Society of Electrophysiology and Kinesiology (ISEK)
  • Place of Presentation: Niagara Falls, Ontario, Canada
  • Year and Date: 2008-06-19
• [Presentation] The relationship between open and closed kinetic chain strength of the lower limb and jumping performance in the anterior cruciate ligament deficient subjects (2008)
  • Author(s): Tohyama H
  • Organizer: The XVII Congress of International Society of Electrophysiology and Kinesiology
  • Place of Presentation: Niagara Falls, Ontario, Canada
  • Year and Date: 2008-06-19
• [Presentation] Synovium-derived fibroblast transplantation possibly deteriorates mechanical properties of the regenerated tissue in the patellar tendon after the harvest of its central one-third portion (2008)
  • Author(s): Tohyama H, Okamoto S, Hayashi K, Yasuda K.
  • Organizer: International Symposium on Ligaments & Tendons VIII
  • Place of Presentation: Stanford University, CA, U.S,A
  • Year and Date: 2008-03-01
• [Presentation] Synovium-derived fibroblast transplantation possibly deteriorates mechanical properties of the regenerated tissue in the patellar tendon after the harvest of its central one-third portion (2008)
  • Author(s): Tohyama H
  • Organizer: International Symposium on Ligaments & Tendons VIII
  • Place of Presentation: Stanford University, CA, U.S.
  • Year and Date: 2008-03-01
• [Presentation] The implantation of autologous synovial tissue-derived fibroblasts after TGF-beta stimulation Inhibits mechanical and ultrastructural deterioration of the ACL after the in situ freeze-thaw treatment (2007)
  • Author(s): Tohyama H., Okuizumi T., Kondo E., Nakamura H., Yasuda K.
  • Organizer: The 6th biennial congress of International Society of Arthroscopy, Knee, and Orthopaedic Sports Medicine
  • Place of Presentation: Florence, Italy
  • Year and Date: 2007-05-29
• [Presentation] The implantation of autologous synovial tissue-derived fibroblasts after TGF-beta stimulation inhibits mechanical and ultrastructural deterioration of the ACL after the in situ freeze-thaw treatment (2007)
  • Author(s): Tohyama H
  • Organizer: ISAKOS 6th Biennial Congress
  • Place of Presentation: Florence, Italy
  • Year and Date: 2007-05-29
• [Presentation] The effect of cytokine inactivation on stress-deprived patellar tendons tendons (2007)
  • Author(s): Tohyama H., Kondo E. , Miyatake S., Katsura T., Yasuda K.
  • Organizer: the 7th International Symposium on Ligaments & Tendons
  • Place of Presentation: La Jolla, Carifornia, U.S.A
  • Year and Date: 2007-02-10
• [Book] 後十字靱帯二重束再建術(安田和則編 : OS NOW Instruction No.8 スポーツによる膝・足関節靱帯損傷の治療) (2008)
  • Author(s): 遠山晴一, 安田和則
  • Publisher: メジカルビュー, 東京
• [Book] 靱帯・腱(岩谷 力ほか編 : 運動器リハビリテーションクルズス) (2008)
  • Author(s): 遠山晴一, 安田和則
  • Publisher: 南江堂, 東京
• [Book] 力とモーメント, 関節にかかる負荷(越智隆弘編 : 最新整形外科大系 運動器の生物学と生体力学) (2008)
  • Author(s): 遠山晴一, 安田和則
  • Publisher: 中山書店, 東京
• [Book] Growth Factors and Other New Methods for Graft Healing Enhancement(Chadwick Prodromos, Charles Brown, Freddie Fu, edt. : THE ANTERIOR CRUCIATE LIGAMENT : RECONSTRUCTION AND BASIC SCIENCE) (2007)
  • Author(s): Tohyama H., Yasuda K.
  • Publisher: WB Saunders Co
• [Book] ジャンパー膝(山口 撤、北原光夫、福井次矢編 : 今日の治療指針2007) (2007)
  • Author(s): 遠山晴一
  • Publisher: 医学書院, 東京
• [Book] 半月板切除(越智隆弘編 : 最新整形外科大系 膝関節・大腿) (2006)
  • Author(s): 遠山晴一, 安田和則
  • Publisher: 中山書店, 東京
• [Book] 治癒促進のための前十字靱帯再建膝への成長因子の応用(宗田 大編 : 実践すぐに役立つ膝靱帯損傷 診断・治療マニュアル) (2006)
  • Author(s): 遠山晴一, 安田和則
  • Publisher: 全日本病院出版, 東京
• [Book] 膝関節の診察(守屋秀繁, 糸満盛憲, 内田淳正, 荻野利彦, 黒坂昌弘, 戸山芳昭編 : 整形外科診療実践ガイド) (2006)
  • Author(s): 遠山晴一, 安田和則
  • Publisher: 文光堂, 東京