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

作者：Hikichi Yuichi^*; Yoshimura Koji; Takigawa Masaharu

来源：Biochemical and Biophysical Research Communications, 2009, 386(2): 294-299.

DOI：10.1016/j.bbrc.2009.06.052

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

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.

• 出版日期2009-8-21