Regulation of the osteophyte formation in knee osteoarthritis by the management of the mesenchymal synovial cell differentiation via synovial perlecan expression

• Project/Area Number: 24592281
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Juntendo University
• Principal Investigator: ISHIJIMA Muneaki 順天堂大学, 医学(系)研究科(研究院), 准教授 (70365576)
• Co-Investigator(Kenkyū-buntansha): HIRASAWA Eri (ARIKAWA Eri) 順天堂大学大学院, 医学研究科・老人性疾患病態・治療研究センター, 先任准教授 (50245718)
• Co-Investigator(Renkei-kenkyūsha): SEKIYA Ichiro 東京医科歯科大学大学院, 整形外科 軟骨再生学, 教授 (10345291)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 変形性膝関節症 / パールカン / 滑膜間葉系細胞 / 骨棘 / 滑膜 / 間葉系幹細胞 / 変形性関節症

Outline of Final Research Achievements

Osteophyte associated with knee osteoarthritis (OA) is a bony outgrowth formed at the margins of the affected joint through endochondral ossification-like processes. However, its mechanism and pathogenesis are unclear. Perlecan (Hspg2), a heparan sulfate proteoglycan, is expressed in many extracellular tissues and plays critical roles in skeletal development and diseases. The aim of the present study is to identify the role of synovial perlecan in osteophyte formation using perinatal lethality rescued perlecan-knockout mice (Hspg2-/--Tg) wherein perlecan expression is lacking in the synovial and other tissues, except for cartilage. In this study, the osteophyte formation in Hspg2-/--Tg mice was significantly reduced in comparison to that in control mice. In addition, we established a primary mouse synovial cell culture method, which may shed light on the mechanistic insight into the role of synovial perlecan in the chondrogenic differentiation of the the synovial mesenchymal cells.

Research Products

• [Journal Article] Synovial perlecan is required for osteophyte formation in knee osteoarthritis (2013)
  • Author(s): Kaneko H, Ishijima M, Futami I, Ichikawa N, Yamada Y, Kurosawa H, Kaneko K, Arikawa-Hirasawa E
  • Journal Title: Matrix Biol Volume: 32 Issue: 3-4 Pages: 178-187
  • DOI: 10.1016/j.matbio.2013.01.004
  • Peer Reviewed
• [Journal Article] Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation. (2012)
  • Author(s): Ishijima M
  • Journal Title: Matrix Biol. Volume: 31(4) Issue: 4 Pages: 234-45
  • DOI: 10.1016/j.matbio.2012.02.006
  • Peer Reviewed
• [Journal Article] Isolation and characterization of multipotential mesenchymal cells from the mouse synovium. (2012)
  • Author(s): Futami I
  • Journal Title: PLoS One. Volume: 7(9) Issue: 9 Pages: e45517-e45517
  • DOI: 10.1371/journal.pone.0045517
  • Peer Reviewed
• [Presentation] パールカンはSOX9遺伝子発現制御を介して滑膜間葉系細胞の軟骨分化誘導を制御する (2015)
  • Author(s): 定月亮，石島旨章，金子晴香，羽田晋之介，木下真由子，金子和夫，平澤恵理
  • Organizer: 第47回日本結合組織学会学術大会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-15 – 2015-05-16
• [Presentation] パールカンによる滑膜間葉系細胞の維持ならびに分化誘導の制御 (2014)
  • Author(s): 定月 亮, 石島 旨章, 金子 晴香, 二見 一平, 劉 立足, Yusup Anwarjan, 羽田 晋之介, 木下 真由子, Goldring Mary B., Yamada Yoshihiko, 平澤 恵理, 金子 和夫
  • Organizer: 第29回日本整形外科学会基礎学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 2014-10-09
• [Presentation] Role of perlecan in chondrogenic, osteogenic and adipogenic differentiation of synovial mesenchymal calls (2014)
  • Author(s): R. Sadatsuki, H. Kaneko, I. Futami, S. Hada, K. L. Culley, M. Otero, C. Dragomir, M. Kinoshita, M.B. Goldring, Y. Yamada, E. Arikawa-Hirasawa, K. Kaneko, M. Ishijima
  • Organizer: 2014Osteoarthritis Research Society International
  • Place of Presentation: パリ
  • Year and Date: 2014-04-24 – 2014-04-27