The role of heparan sulfate endosulfatase (Sulf-1) for intervertebral disc degeneration

• Project/Area Number: 25462316
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka Medical College
• Principal Investigator: Neo Masashi 大阪医科大学, 医学部, 教授 (80311736)
• Co-Investigator(Kenkyū-buntansha): OTSUKI Shuhei 大阪医科大学, 医学部, 助教 (20589840)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 椎間板 / ヘパラン硫酸 / II型コラーゲン / Smad2/3 / 変性 / 加齢 / ヘパラン硫酸脱硫酸酵素 / Sulf

Outline of Final Research Achievements

Intervertebral disc degeneration is a prevalent disease and contributes to aging effects. The treatment of disc degeneration has been researched, and some growth factors such as OP1 and FGF18 had reported the potential of disc regeneration. However, the mechanism of disc degeneration is still to be investigated. We elucidated heparan sulfate endosulfatase (Sulf-1) expression in disc with aging and the disc degeneration in Sulf-1 knockout mice were compared with C57BL6 wild type mice in histological analysis. Finally, we investigated type II collagen expression in vitro supplemented with Sulf-1 and determined the effect of TGFβ Smad2/3 or BMP4 Smad1/5 cell signaling pathway. This study demonstrated Sulf-1 regulated TGFβ Smad2/3 cell signaling and critical for disc homeostasis by regulating type II collagen expression.