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

doi:10.1016/j.febslet.2008.07.036

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 journal › Article › peer-review

29 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 language	English
Pages (from-to)	2945-2949
Number of pages	5
Journal	FEBS Letters
Volume	582
Issue number	19
DOIs	https://doi.org/10.1016/j.febslet.2008.07.036
Publication status	Published - 2008 Aug 20
Externally published	Yes

Keywords

ADAMTS4
Aggrecanase
Calcium pentosan polysulfate
Cartilage
Destruction
Inhibition
Osteoarthritis

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2008.07.036

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

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.",

keywords = "ADAMTS4, Aggrecanase, Calcium pentosan polysulfate, Cartilage, Destruction, Inhibition, Osteoarthritis",

author = "Masayuki Takizawa and Taku Yatabe and Aiko Okada and Miyuki Chijiiwa and Satsuki Mochizuki and Peter Ghosh and Yasunori Okada",

year = "2008",

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language = "English",

volume = "582",

pages = "2945--2949",

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T1 - Calcium pentosan polysulfate directly inhibits enzymatic activity of ADAMTS4 (aggrecanase-1) in osteoarthritic chondrocytes

AU - Takizawa, Masayuki

AU - Yatabe, Taku

AU - Okada, Aiko

AU - Chijiiwa, Miyuki

AU - Mochizuki, Satsuki

AU - Ghosh, Peter

AU - Okada, Yasunori

PY - 2008/8/20

Y1 - 2008/8/20

N2 - 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.

AB - 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.

KW - ADAMTS4

KW - Aggrecanase

KW - Calcium pentosan polysulfate

KW - Cartilage

KW - Destruction

KW - Inhibition

KW - Osteoarthritis

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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