Role of Sulf in Cartilage Metabolism

• Project/Area Number: 22890217
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Osaka Medical College
• Principal Investigator: OTSUKI Shuhei 大阪医科大学, 医学部, 助教 (20589840)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥2,912,000 (Direct Cost: ¥2,240,000、Indirect Cost: ¥672,000); Fiscal Year 2011: ¥1,469,000 (Direct Cost: ¥1,130,000、Indirect Cost: ¥339,000); Fiscal Year 2010: ¥1,443,000 (Direct Cost: ¥1,110,000、Indirect Cost: ¥333,000)
• Keywords: Sulf / ヘパラン硫酸 / 加齢 / 変形性関節症 / 軟骨 / 荷重負荷 / 軟骨変性 / FGF2

Research Abstract

Abnormally increased mechanical load due to varus deformity is associated with cartilage degradation in the medial condyle. Interestingly, the tissue damage caused by mechanical stress activates a cellular response that leads to proliferation of STRO-1positive progenitor cells and cluster formation. On the other hand, thick non-degenerated cartilage in the lateral compartment that experiences reduced load due to varus deformity shows low-density single chondrocytes that appear to have reduced proliferative and biosynthetic activity. Appropriate mechanical stress appears critical for maintaining cartilage homeostasis and early restoration of normal mechanical load in both compartments of the knee may prevent cell and tissue damage.

Research Products

• [Journal Article] Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways. (2010)
  • Author(s): Otsuki S, Hanson SR, Miyaki S, Grogan SP
  • Journal Title: Proc Natl Acad Sci U S A Volume: 107 Pages: 10202-7
  • Peer Reviewed
• [Journal Article] Cartilage cell clusters. (2010)
  • Author(s): Lotz MK, Otsuki S.Grogan SP, D'Lima DD
  • Journal Title: Arthritis Rheum Volume: 62 Pages: 2206-10
  • Peer Reviewed
• [Journal Article] Glucosamine-6-sulfamate analogues of heparan sulfate as inhibitors of endosulfatases. (2010)
  • Author(s): Schelwies M, Brinson D, Otsuki S, Hong YH, Lotz MK, Wong CH, Hanson SR
  • Journal Title: Chembiochem. Volume: 11 Pages: 2393-7
  • Peer Reviewed
• [Journal Article] Tissue neogenesis and STRO-1 expression in immature and mature articular cartilage. (2010)
  • Author(s): Otsuki S, Grogan SP, Miyaki S, Kinoshita M, Asahara H, Lotz M
  • Journal Title: J Orthop Res Volume: 28 Pages: 96-102
  • Peer Reviewed
• [Journal Article] Targeted disruption of cartilage-specific microRNA140 promotes osteoarthritis-like pathology. (2010)
  • Author(s): Miyaki S, Sato T, Inoue A, Otsuki S, Ito Y, Yokoyama S, Kato Y, Takemoto F, Nakasa T, Yamashita S, Takada S, Lotz MK, Ueno-Kudo H, Asahara H.
  • Journal Title: Gene Dev Volume: 24 Pages: 1173-85
  • Peer Reviewed
• [Journal Article] Glucosamine-6-sulfamate analogues of heparan sulfate as inhibitors of endosulfatases. (2010)
  • Author(s): Carames B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M
  • Journal Title: Arthritis Rheum Volume: 62 Pages: 791-801
  • Peer Reviewed
• [Presentation] Cartilage Thickness and Chondrocyte Density in Human Osteoarthritic Knee Joints (2012)
  • Author(s): Otsuki S., et al
  • Place of Presentation: Barcelona Spain
  • Year and Date: 2012-04-25
• [Presentation] CAERTILAGE THICKNESS AND CHONDROCYTE DENSITY IN HUMAN OSTEOARTHRITIC KNEE JOINTS (2012)
  • Author(s): 大槻周平
  • Organizer: 国際関節病学会
  • Place of Presentation: バルセロナ(スペイン)
  • Year and Date: 2012-04-25
• [Presentation] Extracellular sulfatases support cartilage homeostasis by regulating BMP and FGF signaling pathways. (2010)
  • Author(s): Otsuki S, Kinoshita M, Lotz M.
  • Organizer: Osteoarthritis Research Society International
  • Place of Presentation: Brussels, Belgium
  • Year and Date: 2010-09-25