終末糖化産物3(AGE3) 長期間刺激はヒト軟骨細胞のアグリカンとⅡ型コラーゲン産生を低下させる。

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  • Long-term Advanced Glycation End Product 3 (AGE3) Stimulation Reduces Aggrecan and Type II Collagen Production in Human Chondrocytes

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<p>Osteoarthritis (OA) is the most common type of cartilage disease and results from the degradation of the extracellular matrix (ECM) in the joints. Approximately, more than 15 million people suffer from OA in Japan. OA also brings with it an extremely high economic burden due to being the most common form of joint disease.</p><p>Articular cartilage consists of chondrocytes and ECM molecules including aggrecan, type II, IX, and XI collagens, and hyaluronan (HA). Aggrecan and collagen are degraded in OA cartilage due to the activity of matrix metalloproteinases and aggrecanases.</p><p>The accumulation of advanced glycation end products (AGEs) is widely considered as a part of normal aging, especially in long-lived tissues. The present study was aimed to investigate the relationship between the long-term treatment response, of AGE3 effects on chondrocytes. </p><p>Method</p><p>The chondrocyte-like cell line OUMS-27 cells were stimulated with certain doses of AGE3 (1,5,10,20,50,100,200 ug/ml). Total RNA and protein were collected from cultured OUMS-27 cells after 1,2,4,8,16 week. The levels of mRNA and protein expression for aggrecan, MMPs and Collagen were analyzed with quantitative RT-PCR and Western Blot analysis, respectively.</p><p>Result</p><p>When human cartilage-like OUMS-27 cells were cultured with AGE3 for a long period of time (8w), the production capacity of type II collagen and aggrecan was significantly reduced. Particularly at low concentrations of AGE3 (10 ug/ml), the expression level of collagen was decreased and did not change at 50 ug/ml or higher concentration. Furthermore, no statistically significant difference in all concentrations for proteases or inflammatory cytokines were obtained.</p><p>Conclusion</p><p>Prolonged exposure of chondrocytes with AGE3 reduced the expression levels of type II collagen and aggrecan, which are essential for cartilage homeostasis. It is planning to investigate the molecular mechanism of this suppression further.</p>

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