Regulation of osteophyte formation in knee osteoarthritis by modulating the function of perlecan expressed in synovium

• Project/Area Number: 15K20019
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Juntendo University
• Principal Investigator: Kaneko Haruka 順天堂大学, 医学部, 助教 (50445516)
• Research Collaborator: ISHIJIMA Muneaki 順天堂大学, 医学(系)研究科(研究院), 准教授 (70365576)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 変形性膝関節症 / 滑膜 / 骨棘 / パールカン / 軟骨分化

Outline of Final Research Achievements

As the pathology of knee osteoarthritis (knee OA) is diverse, we focused on synovitis and osteophyte formation in the knee OA. The aim of this study was to investigate the role of perlecan expressed in synovium in the early stage of synovitis and osteophyte formation in knee OA. The absence of synovial perlecan suppressed osteophyte formation and enhanced synovitis, although there was no difference in articular cartilage degeneration in the early stage of knee OA. These results suggest that that perlecan plays an important role for not only the cartilage differentiation from synovial mesenchymal cells but also for the synovial inflammation, which may be involved in osteophyte formation.

Research Products

• [Int'l Joint Research] National Institutes of Health/Hospital for Special Surgery(米国)
• [Int'l Joint Research] National Institutes of Health/Hospital for Special Surgery(米国)
• [Journal Article] Serum interleukin 6 levels are associated with depressive state of the patients with knee osteoarthritis irrespective of disease severity (2017)
  • Author(s): Shimura Y, Kurosawa H, Tsuchiya M, Sawa M, Kaneko H, Liu L, Makino Y, Nojiri H, Iwase Y, Kaneko K, Ishijima M
  • Journal Title: Clin Rheumatol Volume: 36 Issue: 12 Pages: 2781-2787
  • DOI: 10.1007/s10067-017-3826-z
  • Peer Reviewed
• [Journal Article] Association of medial meniscal extrusion with medial tibial osteophyte distance detected by T2 mapping MRI in the patients with eraly-stage knee osteoarthritis. (2017)
  • Author(s): Hada S., Ishijima M., Kaneko H., Kinoshita M., Liu L., Sadatusuki R., Futami I., Yusup A., Takamura T., Arita H., Shiozawa J., Aoki T., Takazawa Y., Ikeda H., Aoki S., Kurosawa H., Okada Y. and Kaneko K.
  • Journal Title: Arthritis Res Ther Volume: 19 Issue: 1 Pages: 201-201
  • DOI: 10.1186/s13075-017-1411-0
  • Peer Reviewed / Open Access
• [Journal Article] Perlecan is required for the chondrogenic differentiation of synovial mesenchymal cells through regulation of Sox9 gene expression (2017)
  • Author(s): Sadatsuki R, Kaneko H, Futami I, Kinoshita M, Nonaka R, Culley KL, Otero M, Hada S, Goldring MB, Yamada Y, Kaneko K, Arikawa-Hirasawa E, Ishijima M
  • Journal Title: J Orthop Res Volume: 35 Issue: 4 Pages: 837-46
  • DOI: 10.1002/jor.23318
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Vitamin D status and index representing the detrimental mechanical loading across the knee joint in end-stage knee osteoarthritis representing the detrimental mechanical loading across the knee joint in end-stage knee osteoarthritis. (2017)
  • Author(s): Mayuko Kinoshita, Haruka Kaneko, Muneaki Ishijima, Liu Liz, Ryo Sadatsuki, Shinnosuke Hada, Anwarjan Yusup, Hitoshi Arita, Jun Shiozawa, Takako Aoki, Yoshifumi Tamura, Ryuzo Kawamori, Kazuo Kaneko
  • Organizer: OARSI World Congress 2017
  • Int'l Joint Research
• [Presentation] パールカンが関連する膝滑膜間葉系細胞の遺伝子発現プロファイルの網羅的解析 (2017)
  • Author(s): 有田 均, 金子 晴香, 石島 旨章, 羽田 晋之介, 木下 真由子, 定月 亮, 二見 一平, 塩澤 淳, 平澤 恵理, 金子 和夫
  • Organizer: 第49回日本結合組織学会学術大会
• [Presentation] パールカンにより制御される滑膜間葉系細胞の遺伝子の網羅的解析 (2017)
  • Author(s): 有田 均, 金子 晴香, 石島 旨章, 羽田 晋之介, 木下 真由子, 定月 亮, 二見 一平, 塩澤 淳, 平澤 恵理, 山田 吉彦, 金子 和夫
  • Organizer: 第32回日本整形外科学会基礎学術集会
• [Presentation] パールカンによる滑膜間葉系細胞からの軟骨分化制御 (2016)
  • Author(s): 木下 真由子, 金子 晴香, 石島 旨章, 定月 亮, 二見 一平, 羽田 晋之介, 有田 均, 塩澤 淳, 平澤 恵理, Goldring Mary, 山田 吉彦, 金子 和夫
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡県
  • Year and Date: 2016-10-13
• [Presentation] パールカンによる滑膜間葉系細胞からの軟骨分化制御 (2016)
  • Author(s): 木下 真由子, 石島 旨章, 金子 晴香 定月 亮, 二見 一平, 平澤 恵理, Yamada Yoshihiko, 金子 和夫
  • Organizer: 第48回日本結合組織学会学術大会
  • Place of Presentation: 長崎県
  • Year and Date: 2016-06-24
• [Presentation] Perlecan regulates chondrogenic differentiation from synovial mesenchymal cells via Smad and MAPK signaling pathways (2016)
  • Author(s): Mayuko K, Kaneko H, Sadatsuki R, Futami I, Hada S, Arita H, Shiozawa J, Hirasawa-Arikawa E, Yamada Y, Kaneko K, Ishijima M
  • Organizer: OARSI 2016 World Congress
  • Place of Presentation: Amsterdam, Netherlands
  • Year and Date: 2016-04-01
  • Int'l Joint Research