All-trans retinoic acid-induced ADAM28 degrades proteoglycans in human chondrocytes |
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Authors: | Yuichi Hikichi Koji Yoshimura |
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Affiliation: | a Pharmacology Research Laboratories II, Takeda Pharmaceutical Company Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan b The Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan |
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Abstract: | 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. |
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Keywords: | ADAM28 MMP Osteoarthritis Cartilage destruction Retinoic acid |
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