The Nicotinamide Adenine Dinucleotide (NAD)-Dependent Deacetylase Sirtuin-1 Regulates Chondrocyte Energy Metabolism through the Modulation of Adenosine Monophosphate-Activated Protein Kinase (AMPK) in Osteoarthritis(OA)
Journal of Arthritis(2017)
Abstract
To clarify how the osteoarthritis (OA)-induced catabolic factor interleukin (IL)-1β affects chondrocyte energy metabolism, and especially to define the downstream pathway linking nicotinamide adenine dinucleotide (NAD)- dependent deacetylase Sirtuin-1 (Sirt-1) to energy metabolism in OA chondrocytes. Human isolated from articular cartilage samples patients with OA. The level energy metabolism OA chondrocytes was evaluated by monitoring the activity the energy metabolic sensor, adenosine monophosphate-activated protein kinase (AMPK) and the level production adenosine triphosphate (ATP) in in the presence or absence t IL-1β (10 ng/mL). Effects IL-1β on anabolic and catabolic activities were analyzed by the levels production proteoglycan and matrix metalloproteinase (MMP)-13, respectively. Experiments involving pre-treatment with Sirt-1 inhibitor were also performed to investigate the underlying regulatory mechanism linking Sirt-1 to chondrocyte energy metabolism. IL-1β significantly inhibited the activity AMPK and production of ATP in OA chondrocytes. The energy metabolism disruption mediated by IL-1β was further decreased by pretreatment with Sirt-1 inhibitor in OA chondrocytes. Treatment with IL-1β significantly decreased the level of proteoglycan production and significantly increased the level MMP-13 secretion by chondrocytes. These chondrocyte activities were also reduced by pre-treatment with the Sirt-1 inhibitor in OA chondrocytes. IL-1β inhibits the AMPK - ATP energy metabolic pathway in OA chondrocytes. Our findings also suggest that Sirt-1 activity is involved in anabolic and catabolic cellular activities and that Sirt-1 modulates ATP production through functional regulation the energy sensor AMPK in chondrocytes.
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Key words
chondrocyte energy metabolism,osteoarthritisoa,nicotinamide adenine dinucleotide,protein kinase,monophosphate-activated
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