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The gene expression of  mTOR , autophagy-related  ULK1 ,  caspase 3 , CDK-inhibitor  p21 , and  TNF    α   was measured in the peripheral blood of osteoarthritic (OA) patients at different stages of the disease aiming to establish a gene expression profile that might indicate the activity of the disease and joint destruction. Whole blood of 65 OA outpatients, 27 end-stage OA patients, 27 healthy volunteers, and knee articular cartilages of 28 end-stage OA patients and 26 healthy subjects were examined. OA outpatients were subjected to clinical testing, ultrasonography, and radiographic and WOMAC scoring. Protein levels of p70-S6K, p21, and caspase 3 were quantified by ELISA. Gene expression was measured using real-time RT-PCR. Upregulation of  mTOR  gene expression was observed in PBMCs of 42 OA outpatients (“High  mTOR  expression subset”) and in PBMCs and articular cartilages of all end-stage OA patients. A positive correlation between  mTOR  gene expression in PBMCs and cartilage was observed in the end-stage OA patients. 23 OA outpatients in the “Low  mTOR  expression subset” exhibited significantly lower  mTOR  gene expression in PBMCs compared to healthy controls. These “Low  mTOR ” subset subjects experienced significantly more pain upon walking, and standing and increased total joint stiffness versus “High  mTOR ” subset, while the latter more often exhibited synovitis. The protein concentrations of p70-S6K, p21, and caspase 3 in PBMCs were significantly lower in the “Low” subset versus “High” subset and end-stage subjects. Increases in the expression of  mTOR  in PBMCs of OA patients are related to disease activity, being associated with synovitis more than with pain.

arthritis

Differences in Mammalian Target of Rapamycin Gene Expression in the Peripheral Blood and Articular Cartilages of Osteoarthritic Patients and Disease Activity