Effects of Leptin on Proliferation, Anabolic and Catabolic Metabolism in Chondrocytes / 대한정형외과연구학회지

ABSTRACT

PURPOSE: Leptin may play an important role in the pathophysiology of osteoarthritis. However, the effect of letpin on the anabolic and catabolic metabolisms in chondrocytes remains unclearly elucidated. Therefore, the purpose of this study was to investigate the effect of leptin on proliferation, anabolic and catabolic metabolism of chondrocyte using ATDC5 chondrogenic cell line. MATERIALS AND METHODS: The effects of leptin on chodnrocyte proliferation, anabolic and catabolic meatabolism were examined in ATDC5 cells treated with leptin at varying concentrations(10, 100, 300, 600 ng/ml) for 24, 48, and 72 hours. The cell proliferation was evaluated by MTT assay. The anabolic and catabolic activities were assayed by RT-PCR for transforming growth factor-beta(TNF-alpha), proteoglycan-4 (PRG4), type- I collagen (type- I Col) and tumor necrosis factor-beta(TNF-alpha), matrix metalloproteinase -2 (MMP-2), respectively. RESULTS: Leptin treatment did not influence cell proliferation of chondrocyte regardless of concentration. TGF-beta expression was increased until 48 hours of leptin treatment compared to controls. Especially, it was significantly increased in leptin of 10 ng/ml and 100 ng/ml (P<0.05). PRG4 expression was not different between letpin treatment and controls. Type-I Col expression was decreased in dose- and time-dependent manner. Leptin of 10ng/ml significantly inhibited MMP-2 and TNF-alpha expressions compared to controls (P<0.05). CONCLUSION: This study shows that leptin at low concentration increases TGF-beta expression, but inhibits the expression of TNF-alpha and MMP-2. Also this study shows that leptin do not affect the cell proliferation of chondrocytes. These results suggest that leptin at low or physiological level contributes to the prevention of cartilage damage by stimulating anabolic activity and inhibiting catabolic activity of chondrocyte rather than chondrocyte regeneration by increasing cell proliferation.