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

摘要

The gene expression ofmTOR, autophagy-relatedULK1,caspase 3, CDK-inhibitorp21, andTNFαwas 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 ofmTORgene expression was observed in PBMCs of 42 OA outpatients (“HighmTORexpression subset”) and in PBMCs and articular cartilages of all end-stage OA patients. A positive correlation betweenmTORgene expression in PBMCs and cartilage was observed in the end-stage OA patients. 23 OA outpatients in the “LowmTORexpression subset” exhibited significantly lowermTORgene expression in PBMCs compared to healthy controls. These “LowmTOR” subset subjects experienced significantly more pain upon walking, and standing and increased total joint stiffness versus “HighmTOR” 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 ofmTORin PBMCs of OA patients are related to disease activity, being associated with synovitis more than with pain.