Development of human neutralizing antibody to ADAMTS4 (aggrecanase-1) and ADAMTS5 (aggrecanase-2)

Aya Shiraishi, Satsuki Mochizuki, Akira Miyakoshi, Kanehisa Kojoh, Yasunori Okada

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

ADAMTS4 (aggrecanase-1) and ADAMTS5 (aggrecanase-2), members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family, are considered to play a key role in aggrecan degradation of articular cartilage in human osteoarthritis. Here, we developed a neutralizing antibody to these aggrecanases by screening human combinatorial antibody library. Among the five candidate antibodies, one antibody was immunoreactive with both ADAMTS4 and ADAMTS5, showing no or negligible cross-reactivity with 10 different related metalloproteinases of the ADAMTS, ADAM (a disintegrin and metalloproteinase) and MMP (matrix metalloproteinase) gene families. This antibody almost completely and partially inhibited aggrecanase activity of ADAMTS4 and ADAMTS5, respectively. It also suppressed the aggrecanase activity derived from interleukin-1-stimulated osteoarthritic chondrocytes. These data demonstrate that the antibody is specific to ADAMTS4 and ADAMTS5 and inhibits their aggrecanase activity at molecular and cellular levels, and suggest that this antibody may be useful for treatment of pathological conditions such as osteoarthritis.

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume469
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

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Keywords

  • ADAMTS4
  • ADAMTS5
  • Aggrecanase
  • Cartilage
  • Human antibody
  • Osteoarthritis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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