Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes

Masayuki Takizawa, Taku Yatabe, Aiko Okada, Miyuki Chijiiwa, Satsuki Mochizuki, Peter Ghosh, Yasunori Okada

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Aggrecanases that include ADAMTS1, 4, 5, 8, 9 and 15 are considered to play key roles in aggrecan degradation in osteoarthritic cartilage. Here we demonstrate that calcium pentosan polysulfate (CaPPS) directly inhibits the aggrecanase activity of ADAMTS4 without affecting the mRNA expression of the ADAMTS species in interleukin-1α-stimulated osteoarthritic chondrocytes. Synthetic peptides corresponding to specific regions of the thrombospondin type 1 repeat, cysteine-rich or spacer domain of ADAMTS4 inhibit the binding to immobilized CaPPS. These data suggest that CaPPS could function as chondroprotective agent for the treatment of osteoarthritis by inhibition of ADAMTS4 through interaction with the C-terminal ancillary domain.

Original languageEnglish
Pages (from-to)2945-2949
Number of pages5
JournalFEBS Letters
Volume582
Issue number19
DOIs
Publication statusPublished - 2008 Aug 20

Keywords

  • ADAMTS4
  • Aggrecanase
  • Calcium pentosan polysulfate
  • Cartilage
  • Destruction
  • Inhibition
  • Osteoarthritis

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes'. Together they form a unique fingerprint.

  • Cite this

    Takizawa, M., Yatabe, T., Okada, A., Chijiiwa, M., Mochizuki, S., Ghosh, P., & Okada, Y. (2008). Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes. FEBS Letters, 582(19), 2945-2949. https://doi.org/10.1016/j.febslet.2008.07.036