The role of fibrinolytic system during bone repair in diabetes mic

• Project/Area Number: 15K08195
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Kindai University
• Principal Investigator: OKADA Kiyotaka 近畿大学, 医学部, 准教授 (20185432)
• Co-Investigator(Kenkyū-buntansha): 河尾 直之 近畿大学, 医学部, 講師 (70388510) ; 梶 博史 近畿大学, 医学部, 教授 (90346255)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨修復 / SDF-1 / プラスミノーゲン / 骨髄幹細胞 / 組織線溶 / 骨損傷 / 糖尿病 / 線溶系

Outline of Final Research Achievements

We previously revealed that stromal cell-derived factor-1 (SDF-1) is involved in the changes in the number of bone marrow stem cells during the bone repair process in mice. Moreover, we reported that plasminogen (Plg) deficiency delays bone repair. We investigated the roles of Plg in the changes in bone marrow stem cells during bone repair. Plg deficiency significantly blunted a decrease in the number of HSCs after bone injury in mice. Plg deficiency significantly blunted the number of SDF-1- and Osterix-double-positive cells in the endosteum around the lesion as well as mRNA levels of SDF-1 and transforming growth factor-b (TGF-b) elevated by bone injury. TGF-b signaling inhibition significantly blunted a decrease in the number of HSCs after bone injury. The present study showed that Plg is critical for the changes in bone marrow HSCs, TGF-b and SDF-1 at the damaged site during bone repair in mice.

Research Products

• [Journal Article] Role of macrophages and plasminogen activator inhibitor-1 in delayed bone repair in diabetic female mice. (2018)
  • Author(s): Shimoide T, Kawao N, Tamura Y, Okada K, Horiuchi Y, Okumoto K, Kurashimo S, Ishida M, Tatsumi K, Matsuo O, Kaji H.
  • Journal Title: Endocrinology Volume: 159 Pages: 1875-1885
  • Peer Reviewed / Open Access
• [Journal Article] A synthetic peptide derived from staphylokinase enhances FGF-2-induced skin wound healing in mice. (2017)
  • Author(s): Okada K, Kojima K, Okumoto K, Kawao N, Matsuo O, Kaji H.
  • Journal Title: Thromb Res Volume: 157 Pages: 7-8
  • Peer Reviewed / Open Access
• [Journal Article] Role of plasminogen activator inhibitor-1 in glucocorticoid-induced muscle change in mice. (2017)
  • Author(s): Tamura Y, Kawao N, Shimoide T, Okada K, Matsuo O, Kaji H.
  • Journal Title: J Bone Miner Metab Volume: 印刷中 Issue: 2 Pages: 148-156
  • DOI: 10.1007/s00774-017-0825-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stromal cell-derived factor-1 mediates changes of bone marrow stem cells during bone repair process. (2016)
  • Author(s): Okada K, Kawao N, Yano M, Tamura Y, Kurashimo S, Okumoto K, Kojima K, Kaji H.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 310
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of osteoclasts in the heterotopic ossification enhanced by fibrodysplasia ossificans progressiva-related activin-like kinase 2 mutation in mice. (2015)
  • Author(s): Kawao N, Kaji H, et al.
  • Journal Title: J Bone Miner Metab Volume: Epub ahead of print Issue: 5 Pages: 1-9
  • DOI: 10.1007/s00774-015-0701-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 骨損傷後の骨髄造血幹細胞変化におけるプラスミノーゲン/SDF-1/TGF-b系の役割 (2018)
  • Author(s): 岡田清孝、河尾直之、児嶋耕太郎、蔵下伸治、奥本勝美、辰巳公平、石田昌義、松尾 理、梶 博史
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] 糖尿病による骨修復遅延における造血幹細胞・マクロファージの役割 (2018)
  • Author(s): 下出孟史、河尾直之、田村行識、岡田清孝、蔵下伸治、奥本勝美、辰巳公平、松尾 理、梶 博史
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] Roles of plasminogen in the alterations in bone marrow hematopoietic stem cells during bone repair. (2017)
  • Author(s): 児嶋耕太郎、岡田清孝、河尾直之、蔵下伸治、奥本勝美、辰巳公平、石田昌義、松尾 理、梶 博史.
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松（浜松市）
  • Year and Date: 2017-03-28
• [Presentation] 骨損傷により誘導される骨髄造血幹細胞変化におけるSDF-1とプラスミノーゲンの連関. (2017)
  • Author(s): 岡田清孝、河尾直之、児嶋耕太郎、蔵下伸治、奥本勝美、辰巳公平、石田昌義、松尾 理、梶 博史.
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター（仙台市）
  • Year and Date: 2017-03-07
• [Presentation] マクロファージは糖尿病による骨修復遅延に関与する (2017)
  • Author(s): 下出孟史、田村行識、岡田清孝、河尾直之、蔵下伸治、奥本勝美、辰巳公平、石田昌義、梶 博史
  • Organizer: 第35回日本骨代謝学会学術集会
• [Presentation] 骨損傷後のSDF-1による骨髄造血幹細胞誘導におけるプラスミノーゲンの関与. (2016)
  • Author(s): 岡田清孝、河尾直之、児嶋耕太郎、蔵下伸治、奥本勝美、田村行識、下出孟史、松尾 理、梶 博史.
  • Organizer: 第34回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪市）
  • Year and Date: 2016-07-20
• [Presentation] Roles of bone marrow stem cells during bone repair process (2016)
  • Author(s): 岡田清孝、河尾直之、田村行識、皆島 健、蔵下伸治、奥本勝美、児嶋耕太郎、梶 博史
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンシェンセンター（札幌市）
  • Year and Date: 2016-03-22
• [Presentation] SDF-1/CXCR4系による骨修復再生過程での骨髄幹細胞の分化誘導機構 (2015)
  • Author(s): 岡田清孝、河尾直之、田村行識、蔵下伸治、奥本勝美、児嶋耕太郎、梶 博史
  • Organizer: 第108回近畿生理学談話会
  • Place of Presentation: 近畿大学東大阪キャンパス（東大阪市）
  • Year and Date: 2015-10-24
• [Presentation] 骨修復過程に誘導される骨髄幹細胞変化とSDF-1の役割 (2015)
  • Author(s): 岡田清孝、河尾直之、田村行識、矢野昌人、蔵下伸治、奥本勝美、児嶋耕太郎、梶博史
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザ（東京）
  • Year and Date: 2015-07-23
• [Presentation] 骨修復・再生過程における骨髄幹細胞の役割 (2015)
  • Author(s): 岡田清孝、河尾直之、田村行識、矢野昌人、蔵下伸治、奥本勝美、児嶋耕太郎、梶 博史
  • Organizer: 第36回日本炎症・再生医学会
  • Place of Presentation: 虎の門ヒルズフォーラム（東京）
  • Year and Date: 2015-07-21