Effects Of Dexmedetomidine At Different Concentrations On Inducible Nitric Oxide Synthase In Chondrocytes

Backgroud and purposeOsteoarthritis is the most common chronic degenerative joint disease in the world,which can cause pain and disability and seriously affect the quality of life of patients.Cartilage,subchondral bone,synovium,and systemic inflammation play important roles in the pathogenesis of osteoarthritis.Inducible nitric oxide synthase and its synthesized NO play an important role in osteoarthritis by promoting inflammation,promoting chondrocyte apoptosis and extracellular matrix degradation,inhibiting extracellular matrix synthesis,and aggravating synovitis.Dexmedetomidine is a highly selectiveα₂ adrenergic receptor agonist,and has been found to have anti-inflammatory,sympathetic,organ protection and analgesic effects in many studies.Whether dexmedetomidine plays a role in osteoarthritis by regulating the production of chondrocyte iNOS/NO should be fully elucidated.In this study,we investigated the effects of different concentrations of dexmedetomidine（0.1μM、1μM、10μM）on iNOS activity and NO production in osteoarthritis cell models.MethodOsteoarthritis cell model was established by stimulating rat knee chondrocytes with Recombinant Rat IL-1β（10 ng/mL）.The experiment was divided into 5 groups:○1 control group（control）,○2 IL-1βstimulation group（M）,○3 IL-1βstimulation+low concentration（0.1μM）dexmedetomidine（Dex）group（M+DL）,○4 IL-1βstimulation+medium concentration（1μM）of dexmedetomidine group（M+DM）,○5IL-1βstimulation+high concentration（10μM）of dexmedetomidine group（M+DH）.The CCK8 assay was used to determine the cytotoxicity of dexmedetomidine at each concentration.The NO level of each group of cell culture fluid was evaluated using a NO detection kit.The iNOS detection kit was used to evaluate the activity of iNOS in each group of cell proteins.Results（1）All three concentrations（0.1μM、1μM、10μM）of dexmedetomidine were non-cytotoxic to chondrocytes.（2）IL-1βsignificantly increased the activity of iNOS and NO production in chondrocytes.Dexmedetomidine can inhibit the activity of iNOS and NO production in chondrocytes induced by IL-1βin a concentration-dependent manner.ConclusionDexmedetomidine can inhibit IL-1β-induced chondrocyte iNOS activity and NO production in a concentration-dependent manner,reduce chondrocyte damage,and delay the progress of osteoarthritis.