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)
| Autor: | Koh Terauchi, Hisateru Niki, Kanaka Yatabe, Hiroto Fujiya, Hajime Kobayashi, Kazuo Yudoh, Naoko Yui, Haruki Musha, Toshikazu Kamada |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adenosine monophosphate medicine.medical_specialty Anabolism biology Sirtuin 1 AMPK Nicotinamide adenine dinucleotide Chondrocyte 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry Internal medicine medicine biology.protein NAD+ kinase Adenosine triphosphate |
| Zdroj: | Journal of Arthritis. |
| ISSN: | 2167-7921 |
| DOI: | 10.4172/2167-7921.1000238 |
| Popis: | 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 chondrocytes were isolated from articular cartilage samples of patients with OA. The level of energy metabolism of OA chondrocytes was evaluated by monitoring the activity of the energy metabolic sensor, adenosine monophosphate-activated protein kinase (AMPK) and the level of production of adenosine triphosphate (ATP) in chondrocytes in the presence or absence of t IL-1β (10 ng/mL). Effects of IL-1β on anabolic and catabolic activities of chondrocytes were analyzed by the levels of production of 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 of 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 of 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 of the energy sensor AMPK in chondrocytes. |
| Databáze: | OpenAIRE |
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