Role of MIF on the process of fracture healing and the effect of its regulation

• Project/Area Number: 21591909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hokkaido University
• Principal Investigator: ONODERA Shin 北海道大学, 大学院・医学研究科, 客員准教授 (00359481)
• Co-Investigator(Kenkyū-buntansha): TOHYAMA Harukazu 北海道大学, 北海道大学病院, 准教授 (60301884) ; YASUDA Kazunori 北海道大学, 大学院・医学研究科, 教授 (20166507)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨折治癒 / マクロファージ遊走阻止因子 / ノックアウトマウス / 構造特性 / 遺伝子発現 / 骨形態計測 / 力学試験 / 骨髄細胞 / 石灰化

Research Abstract

We investigated the role of macrophage migration inhibitory factor (MIF) on the process of fracture healing using MIF KO mice. In MIF KO mice, the mechanical properties of the fracture callus were decreased at the early stage of fracture healing, which was caused at least in part by the delay in the calcification of osteoid or the decrease in the number of osteoclasts. These were considered to be associated with decreased mRNA expression of MMP-2, MT1-MMP, Cathepsin K, and alkaline phosphatase.

Research Products

• [Journal Article] Induction of spontaneous hyaline cartilage regeneration using a double-network gel : efficacy of a novel therapeutic strategy for an articular cartilage defect (2011)
  • Author(s): Kitamura N, Yasuda K, Ogawa M, Arakaki K, Kai S, Onodera S, Kurokawa T, GongJP
  • Journal Title: Am J Sports Med. Volume: 39(6) Pages: 1160-1169
  • Peer Reviewed
• [Journal Article] Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel : Comparisons with the normal articular cartilage (2011)
  • Author(s): Imabuchi R, Ohmiya Y, Kwon HJ, Onodera S, Kitamura N, Kurokawa T, Gong JP, Yasuda K
  • Journal Title: BMC Musculoskelet Disord Volume: 12 Pages: 213-213
  • NAID: 120005512012
  • Peer Reviewed
• [Journal Article] Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel (2011)
  • Author(s): Yokota M, Yasuda K, Kitamura N, Arakaki K, Onodera S, Kurokawa T, Gong JP
  • Journal Title: BMC Musculoskelet Disord Volume: 12 Pages: 49-49
  • NAID: 120005512013
  • Peer Reviewed
• [Journal Article] Impaired fracture healing in macrophage migration inhibitory factor-deficient mice (2011)
  • Author(s): Kobayashi T, Onodera S, Kondo K, Tohyama H, Fujiki H, Yokoyama Y, Yasuda K.
  • Journal Title: Osteoporosis Int Volume: 22(6) Pages: 1955-1965
  • Peer Reviewed
• [Journal Article] DNA vaccination targeting macrophage migration inhibitory factor prevents murine experimental colitis (2011)
  • Author(s): Ohkawara T, Koyama Y, Onodera S, Takeda H, Kato M, Asaka M, Nishihira J
  • Journal Title: Clin Exp Immunol Volume: 95 Pages: 531-42
  • Peer Reviewed
• [Journal Article] Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation (2011)
  • Author(s): Arakaki K
  • Journal Title: J Mater Sci Mater Med Volume: 22 Issue: 2 Pages: 417-425
  • DOI: 10.1007/s10856-010-4216-0
  • Peer Reviewed
• [Journal Article] Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel (2011)
  • Author(s): Yokota M
  • Journal Title: BMC Musculoskeletal Disord Volume: 12 Issue: 1 Pages: 49-49
  • DOI: 10.1186/1471-2474-12-49
  • Peer Reviewed
• [Journal Article] Induction of spontaneous hyaline cartilage regeneration using a double-network gel : efficacy of a novel therapeutic strategy for an articular cartilage defect (2011)
  • Author(s): Kitamura N
  • Journal Title: Am J Sports Med Volume: 39 Issue: 6 Pages: 1160-1169
  • DOI: 10.1177/0363546511399383
  • Peer Reviewed
• [Journal Article] DNA vaccination targeting macrophage migration inhibitory factor prevents murine experimental colitis. (2011)
  • Author(s): Ohkawara T
  • Journal Title: Clin Exp Immunol Volume: 163 Pages: 113-122
  • Peer Reviewed
• [Journal Article] In vivo Imaging of Particle-Induced Inflammation and Osteolysis in the Calvariae of NF _κB/luciferase Transgenic Mice. (2011)
  • Author(s): Takahashi K
  • Journal Title: Journal of Biomedicine and Biotechnology Volume: (Epub 2010 Sep 21)
  • Peer Reviewed
• [Journal Article] Joint immobilization inhibits spontaneous hyaline cartilagerege neration induced by a novel double-network gel implantation (2010)
  • Author(s): Arakaki K, Kitamura N, Kurokawa T, Onodera S, Kanaya F, Gong JP, Yasuda K.
  • Journal Title: J Mater Sci Mater Med. Volume: 93 Pages: 1160-1168
  • Peer Reviewed
• [Journal Article] Deficiency of Macrophage Migration Inhibitory Factor Gene Delays Healing of the Medial Collateral Ligament : A Biomechanical and Biological Study (2010)
  • Author(s): Kitayama S, Onodera S, Kondo K, Kobayashi T, Miyatake S, Kitamura N, Tohyama H, Yasuda K
  • Journal Title: Journal of Biomechanics Volume: 44 Pages: 494-500
  • NAID: 120002834758
  • Peer Reviewed
• [Journal Article] In vivo Imaging of Particle-Induced Inflammation and Osteolysis in the Calvariae of NFκB/luciferase Transgenic Mice (2010)
  • Author(s): Takahashi K, Onodera S, Tohyama H, Kwon HJ, Honma K, Yasuda K
  • Journal Title: Journal of Biomedicine and Biotechnology
  • NAID: 120002693632
  • Peer Reviewed
• [Journal Article] Gene expression, glycocalyx assay, and surface properties of human endothelial cells cultured on hydrogel matrix with sulfonic moiety : Effect of elasticity of hydrogel (2010)
  • Author(s): Yang JJ, Yong Mei C, Kurokawa T, Gong JP, Onodera S, Yasuda K
  • Journal Title: Journal of Biomedical Materials Research Volume: Part A 95 Pages: 531-42
  • NAID: 120002758424
  • Peer Reviewed
• [Journal Article] Tunnel location in transparent 3-dimensional CT in anatomic double-bundle anterior cruciate ligament reconstruction with the trans-tibial tunnel technique (2010)
  • Author(s): Inoue M, Tokuyasu S, Kuwahara S, Yasojima N, Kasahara Y, Kondo E, Onodera S, Yasuda K
  • Journal Title: Knee Surg Sports Traumatol Arthrosc Volume: 18 Pages: 176-83
  • Peer Reviewed
• [Journal Article] Gene expression, glycocalyx assay, and surface properties of human endothelial cells cultured on hydrogel matrix with sulfonic moiety : Effect of elasticity of hydrogel. (2010)
  • Author(s): Yang JJ
  • Journal Title: Journal of Biomedical Materials Research : Part A Volume: 95 Pages: 531-542
  • Peer Reviewed
• [Journal Article] Impaired fracture healing in macrophage migration inhibitory factor-deficient mice. (2010)
  • Author(s): Kobayashi T
  • Journal Title: Osteoporosis Int Volume: (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Deficiency of Macrophage Migration Inhibitory Factor Gene Delays Healing of the Medial Collateral Ligament : A Biomechanical and Biological Study. (2010)
  • Author(s): Kitayama S
  • Journal Title: Journal of Biomechanics Volume: 44 Pages: 494-500
  • Peer Reviewed
• [Journal Article] Analysis of Wear Debris from the Metal-on-metal Hip Joint (2009)
  • Author(s): Uo M, Watari F, Asakura K, Katayama N, Onodera S, Tohyama H, Hamada K, OhnukiS
  • Journal Title: Nano Biomedicine Volume: 1 Pages: 133-136
  • Peer Reviewed
• [Journal Article] Enhanced immunoreactivity for basic fibroblast growth factor (FGF2) in the adult rat spinal cord in experimental syringomyelia (2009)
  • Author(s): Miyatake S, Onodera S, Sano T, Katoh S, Ikata T
  • Journal Title: Nano Biomedicine Volume: 1(2) Pages: 167-175
  • NAID: 130004555802
  • Peer Reviewed
• [Journal Article] DNA vaccination against macrophage migration inhibitory factor improves atopic dermatitis in murine models (2009)
  • Author(s): Hamasaka A, Abe R, Koyama Y, Yoshioka N, Fujita Y, Hoshina D, Sasaki M, Hirasawa T, Onodera S, Ohshima S, Leng L, Bucala R, Nishihira J, Shimizu T, Shimizu H
  • Journal Title: J Allergy Clin Immunol Volume: 124(1) Pages: 90-99
  • Peer Reviewed
• [Journal Article] DNA vaccination against macrophage migration inhibitory factor improves atopic dermatitis in murine models. (2009)
  • Author(s): Hamasaka A
  • Journal Title: J Allergy Clin Immunol. 124 Pages: 90-99
  • Peer Reviewed
• [Journal Article] Enhanced immunoreactivity for basic fibroblast growth factor(FGF2)in the adult rat spinal cord in experimental syringomyelia. (2009)
  • Author(s): Miyatake S
  • Journal Title: Nano Biomedicine 1 Pages: 167-175
  • Peer Reviewed
• [Journal Article] Analysis of Wear Debris from the Metal-on-metal Hip Joint. (2009)
  • Author(s): Uo M
  • Journal Title: Nano Biomedicine 1 Pages: 133-136
  • Peer Reviewed
• [Journal Article] Tunnel location in transparent 3-dimensional CT in anatomic doublebundle anterior cruciate ligament reconstruction with the trans-tibial tunnel technique.
  • Author(s): Inoue M
  • Journal Title: Knee Surg Sports Traumatol Arthrosc (In press)
  • Peer Reviewed
• [Presentation] マクロファージ遊走阻止因子遺伝子の欠損が骨折治癒に与える効果 (2011)
  • Author(s): 小林巧、小野寺伸、遠山晴一、近藤英司、安田和則
  • Organizer: 第26回日本整形外科学会基礎学術集会オステオポローシスセミナー
  • Place of Presentation: 前橋市(ベイシア文化ホール)
  • Year and Date: 2011-10-21
• [Presentation] マクロファージ遊走阻止因子遺伝子の欠損が骨折治癒に与える効果 (2011)
  • Author(s): 小林巧
  • Organizer: 第26回日本整形外科学会基礎学術集会
  • Place of Presentation: ベイシア文化ホール(群馬県)
  • Year and Date: 2011-10-21
• [Presentation] In vivo Imaging of Particle-Induced Inflammation and Osteolysis in the Calvariae of NF _κB/luciferase Transgenic Mice. (2010)
  • Author(s): Onodera S
  • Organizer: International symposium on photonic imaging
  • Place of Presentation: Hilton Niseko Village, Niseko, JAPAN
  • Year and Date: 2010-02-10
• [Presentation] In vivo Imaging of Particle-Induced Inflammation and Osteolysis in the Calvariae of NFκB/luciferase Transgenic Mice (2010)
  • Author(s): Onodera S, Tohyama H, Honma K, Yaudsa K
  • Organizer: ORTHOPAEDIC RESEARCH SOCIETY 58th Annual Meeting
  • Place of Presentation: New Orleans, USA
• [Presentation] Role of MIF on the bone turnover and remodeling. (2009)
  • Author(s): Onodera S
  • Organizer: International symposium of MIF
  • Place of Presentation: Hokkaido Information University Sapporo Satellite, Sapporo, Japan
  • Year and Date: 2009-05-20
• [Presentation] Development of a novel DNA vaccine targeting macrophage migration inhibitory factor and its efficacy on murine models of inflammatory diseases. (2009)
  • Author(s): Onodera S
  • Organizer: The 2nd Annual Protein and Peptide Conference
  • Place of Presentation: COEX, Seoul, Korea
  • Year and Date: 2009-04-02
• [Presentation] Role of MIF on the bone turnover and remodelling (2009)
  • Author(s): Onodera S.
  • Organizer: International symposium of MIF
  • Place of Presentation: Sapporo (Hokkaido Information University Sapporo Satellite), Japan
• [Presentation] Development of a novel DNA vaccine targeting macrophage migration inhibitory factor and its efficacy on murine models of inflammatory diseases (2009)
  • Author(s): Onodera S, Koyama Y, Nishihira J, Abe R, Tohyama H, Yasuda K
  • Organizer: The 2nd Annual Protein and Peptide Conference(PepCon-2009)
  • Place of Presentation: Seoul, Korea
• [Book] 人工関節摩耗粉の生体影響と課題、ナノ材料のリスク評価と安全性対策 (2010)
  • Author(s): 小野寺伸
  • Publisher: 亘理文夫監修フロンティア出版、東京