The Function of PPARγ/AMPK/SIRT-1 Pathway in Inflammatory Response of Human Articular Chondrocytes Stimulated by Advanced Glycation End Products

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...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2019/08/01, Vol.42(8), pp.1303-1309
Main Authors: Huang, Hao, Wang, Zhao-jun, Zhang, Hai-bin, Liang, Jian-xia, Cao, Wen-dong, Wu, Qi, He, Chao-peng, Chen, Cheng
Format: Article
Language:English
Subjects:
advanced glycation end product
AMP-activated protein kinase
AMP-Activated Protein Kinases - metabolism
Cartilage, Articular - cytology
Cells, Cultured
chondrocyte
Chondrocytes - metabolism
Glycation End Products, Advanced - metabolism
Humans
Hypoglycemic Agents - pharmacology
Inflammation - metabolism
inflammatory
Pioglitazone - pharmacology
PPAR gamma - metabolism
Signal Transduction
Sirtuin 1 - metabolism
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Summary: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)-1β and tumor necrosis factor (TNF)-α, 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-γ (PPARγ) 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 PPARγ/AMPK/SIRT-1 pathway, which is therefore a potential target in OA therapy.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b19-00036