All-trans retinoic acid-induced ADAM28 degrades proteoglycans in human chondrocytes

Yuichi Hikichi, Koji Yoshimura, Masaharu Takigawa

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


In order to elucidate the mechanism of cartilage degradation in osteoarthritis (OA), we established a cell assay system. Under the stimulation of all-trans retinoic acid (ATRA), the human chondrosarcoma cell line HCS-2/8 increased proteoglycan release from inactivated bovine nasal cartilage (BNC) and the results suggested the involvement of membrane-bound metalloproteinase(s). Therefore, we focused on the induction of a disintegrin and metalloproteinase (ADAM) superfamily upon ATRA stimulation. Of all ADAMs tested, only ADAM28 was induced by ATRA in HCS-2/8 cells and also in human primary chondrocytes. We found that transfection of ADAM28 or its alternatively spliced soluble form augmented proteoglycan release in the cell assay; however, a mutant soluble form in which a portion of the disintegrin domain was deleted did not have proteoglycan-releasing activity, implying the importance of the domain for enzyme localization and substrate recognition for cartilage degradation in OA.

Original languageEnglish
Pages (from-to)294-299
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Aug 21 2009


  • ADAM28
  • Cartilage destruction
  • MMP
  • Osteoarthritis
  • Retinoic acid

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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