Deficiency of macrophage migration inhibitory factor gene delays healing of the damaged tendon matrix: A biomechanical and biological study

Research Project

Project/Area Number	25462319
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Orthopaedic surgery
Research Institution	Hokkaido University
Principal Investigator	Onodera Jun 北海道大学, 大学病院, 助教 (90374511)
Co-Investigator(Kenkyū-buntansha)	近藤英司北海道大学, 医学研究科, 特任教授 (60374724) 安田和則北海道大学, －, 理事・副学長 (20166507)
Research Collaborator	HOSAKA Midori 北海道大学, 医学研究科, 実験助手
Project Period (FY)	2013-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000) Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords	運動器外傷学 / 腱損傷 / 腱マトリクス / マクロファージ
Outline of Final Research Achievements	The role played by macrophage migration inhibitory factor (MIF) in the process of wound healing is controversial. In this study, we hypothesized that the deficiency in MIF gene might delay tendon injury and bone-tendon healing in mice. Biomechanical testing showed that the structural properties were significantly lower in MIF gene-deficient mice (MIFKO) than in wild-type mice (WT). Histologically, healing tissues in MIFKO exhibited prolonged hypertrophy, poor vascularity, and prolonged increase in cell number compared with those in WT and low healing rate between grafted tendon and bone. Levels of matrix metalloproteinase (MMP)-13 mRNA in the healing tissue were significantly lower in MIFKO than in WT at 3 weeks after injury. Taken together, it was suggested that MIFKO exhibited delayed healing of the tendon and the bone-grafted tendon junction.