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Bioengineered ; 13(1): 985-994, 2022 01.
Article in English | MEDLINE | ID: mdl-34968169

ABSTRACT

Osteoarthritis (OA) is a common chronic inflammatory disease associated with aging. Etomidate is an intravenous anesthetic with profound antioxidant and anti-inflammatory effects. We speculated that etomidate might exert a beneficial effect on OA. Herein, we explored the effects of etomidate on interleukin-1ß (IL-1ß)- induced chondrocytes. Our results prove that etomidate ameliorated the IL-1ß-induced oxidative stress in C28/12 chondrocytes by decreasing and increasing the reactive oxygen species (ROS) and glutathione peroxidase (GPx) levels, respectively. Etomidate prevented the IL-1ß-induced increase in the expressions of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13) in C28/I2 chondrocytes at both mRNA and protein levels. It also caused a significant reduction in the percentage of senescence-associated-ß-galactosidase (SA-ß-Gal)-stained chondrocytes, while inducing elevated telomerase activity in IL-1ß-treated C28/I2 chondrocytes. The expression levels of senescence regulators, plasminogen activator inhibitor-1 (PAI-1) and p16, were also inhibited by etomidate in IL-1ß-treated C28/I2 chondrocytes. In addition, etomidate caused the activation of Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), along with upregulated expression levels of phosphorylated AMPKα and phosphorylated acetyl-Co A carboxylase (ACC). Moreover, blockage of AMPK using compound C abolished the protective effects of etomidate on IL-1ß-challenged C28/I2 chondrocytes. Taken together, these results demonstrate that etomidate protected C28/I2 chondrocytes from IL-1ß-induced oxidative stress, ECM degradation, and cellular senescence via activating AMPK signaling.


Subject(s)
Chondrocytes/cytology , Etomidate/pharmacology , Interleukin-1beta/adverse effects , Osteoarthritis/metabolism , Adenylate Kinase/metabolism , Cell Line , Cellular Senescence/drug effects , Chondrocytes/drug effects , Chondrocytes/metabolism , Etomidate/chemistry , Extracellular Matrix/metabolism , Glutathione Peroxidase/metabolism , Humans , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , Models, Biological , Molecular Structure , Osteoarthritis/chemically induced , Osteoarthritis/drug therapy , Osteoarthritis/genetics , Oxidative Stress/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
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