The Function Of Ppar Gamma/Ampk/Sirt-1 Pathway In Inflammatory Response Of Human Articular Chondrocytes Stimulated By Advanced Glycation End Products
BIOLOGICAL & PHARMACEUTICAL BULLETIN(2019)
摘要
Accumulation of advanced glycation end products (AGEs) in the articular cartilage is a major risk factor for osteoarthritis (OA). To determine the mechanistic basis of AGE action in OA, we treated human articular chondrocytes with AGEs, and found that they not only up-regulated the pro-inflammatory cytokines interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha, but also inhibited AMP-activated protein kinase (AMPK) phosphorylation and decreased sirtuin 1 (SIRT-1) levels in a concentration- and time-dependent manner. Pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist restored the inhibited AMPK and SIRT-1 by AGEs. Pre-treatment of the cells with the agonists or antagonists of AMPK and SIRT-1 respectively abolished and augmented the inflammatory state induced by AGEs. Furthermore, AMPK agonist also restored the levels of SIRT-1 in the AGE-stimulated chondrocytes. Our findings indicate AGEs induce an inflammatory response in human articular chondrocytes via the PPAR gamma/AMPK/SIRT-1 pathway, which is therefore a potential target in OA therapy.
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关键词
AMP-activated protein kinase,advanced glycation end product,inflammatory,chondrocyte
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