All-trans retinoic acid-induced ADAM28 degrades proteoglycans in human chondrocytes.
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.
Hikichi
Yuichi
Y
Pharmacology Research Laboratories II, Takeda Pharmaceutical Company Ltd, Tsukuba, Ibaraki 300-4293, Japan. Hikichi_Yuichi@takeda.co.jp
Yoshimura
Koji
K
Takigawa
Masaharu
M
D051722:ADAM Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D001681:Biological Assay; D019556:COS Cells; D002417:Cattle; D002460:Cell Line; D002522:Chlorocebus aethiops; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D045726:Metalloproteases / Q000145:classification / Q000378:metabolism; D010003:Osteoarthritis / Q000201:enzymology / Q000378:metabolism*; D010802:Phylogeny; D011509:Proteoglycans / Q000378:metabolism*; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D011509:Proteoglycans; D014212:Tretinoin; D045726:Metalloproteases; D051722:ADAM Proteins; C410224:ADAM28 protein, human