TSUKAZAKI Tomoo Nagasaki University, Hospital of Medicine and Dentistry, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (50315230)
TSURUMOTO Toshiyuki Nagasaki University, Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (60304937)
|Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥2,300,000 (Direct Cost: ¥2,300,000)
Imbalances between synthesis and degradation of cartilage matrix lead the destruction of articular cartilage. To know the regulation mechanism of cartilage destruction in osteoarthritis, we have examined the effects of insulin-like growth factor (IGF)-I, dexamethasone, and mdomethacin on the action of interleukin (IL)-1β, which is the catabolic factor for cartilage tissue. We performed monolayer or three dimensional culture of chondrocytes. After adding the IL-I β with or without IGF-I, dexamethasone or indomethacin, the concentration of IL-6 and matrix metalloptroteinase (MMP)-3,-9,-13 in the culture medium was measured by ELISA. Further, total RNA was extracted from the cell layer, and the expression of aggrecan, collagen II, IL-6, and MMP-3,9,13 mRNA was measured by RT PCR.
IGF-I induced the expression of aggrecan and collagen II mRNA both in the presence or absence of IL-β. IL-I β increased the expression of IL-6 and MMPs in the protein and mRNA levels. These effects of IL-Iβ was inhibited by dexamethasone and indomethacin but not by IGF-I. These results suggest that different mechanism may exist in the regulation of cartilage destruction.