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Arthritis
Volume 2013 (2013), Article ID 461486, 14 pages
http://dx.doi.org/10.1155/2013/461486
Clinical Study

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

1Clinical Immunology Department, Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia
2Department of Surgery, McGill University, Montreal, QC, Canada H3A OG4
3Osteoarthritis Laboratory, Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia
4Pathomorphology Department, Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia
5Statistics Department, Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia
6Forensic Medicine Service, Moscow City Health Department, Moscow 111020, Russia
7Surgery Department, Research Institute of Rheumatology, Russian Academy of Medical Sciences, Moscow 115522, Russia

Received 28 February 2013; Revised 12 May 2013; Accepted 12 May 2013

Academic Editor: Ruben Burgos-Vargas

Copyright © 2013 Elena V. Tchetina et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The gene expression of mTOR, autophagy-related ULK1, caspase 3, CDK-inhibitor p21, and TNFα 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.