The study of the effect of mechanical stress on the enchondral ossification signals in the ossification of the posterior longitudinal ligament

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10928
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Fukui
• Principal Investigator: Sugita Daisuke 福井大学, 学術研究院医学系部門, 助教 (90596678)
• Co-Investigator(Kenkyū-buntansha): 中嶋 秀明 福井大学, 学術研究院医学系部門, 講師 (10397276) ; 平井 貴之 福井大学, 学術研究院医学系部門, 特別研究員 (30569132)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 後縦靱帯骨化症 / インディアンヘッジホッグ / マイクロアレイ / 内軟骨骨化 / 免疫組織化学的検討

Outline of Final Research Achievements

Ossification of the posterior longitudinal ligament (OPLL) is similar to enchondral ossification. Indian hedgehog (Ihh) and its related signaling are key factors in normal enchondral ossification.In the microarray analysis, Ihh and its related genes showed increased expression levels compared with controls after the 24-hour mechanical strain. In the immunoblotting analysis, Ihh, Sox9, Runx2, Gli2, Gli3, and smoothened (SMO) showed significantly increased their protein expression levels after mechanical strain. In addition, OPLL samples were strongly immunopositive for Ihh, Sox9, Runx2, and Gli3 in the ossification front of OPLL. The expression levels of Ihh and its related genes are upregulated significantly by cyclic tensile strain. These results suggest that cyclic tensile strain induces abnormal activation of Ihh and its related signaling, which might be important in the ossification process in OPLL.

Free Research Field

脊椎外科

Academic Significance and Societal Importance of the Research Achievements

後縦靱帯骨化症(OPLL)の骨化巣の発生や進展機序は未だ不明である。治療法としては対症的な薬物療法か、進行例では神経症状を緩和するための外科的な治療法が存在するが、骨化巣が摘出できるのは限られた一部の症例であり、また、残存した骨化巣の進展による神経症状の再増悪も起こりえる。もしもOPLLの骨化巣進展の機序が解明できれば、骨化巣の進展を制御できる内科的な治療法の開発の一端を担える可能性があると考える。