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

研究成果: Article査読

29 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2945-2949
ページ数5
ジャーナルFEBS Letters
582
19
DOI
出版ステータスPublished - 2008 8月 20

ASJC Scopus subject areas

  • 生物理学
  • 構造生物学
  • 生化学
  • 分子生物学
  • 遺伝学
  • 細胞生物学

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