PREDICTION OF THE COURSE OF OSTEOARTHROSIS FROM mTOR (MAMMALIAN TARGET OF RAPAMYCIN) GENE EXPRESSION

Abstract

Objective: To study whether the course of the disease can be predicted in patients with osteoarthrosis (OA), by monitoring mTOR (Mammalian Target Of Rapamycin) gene expression in their blood. Material and methods. The investigation was conducted on the peripheral blood samples from 33 outpatients (58.4±7.4 years) with OA; 10 patients (56.5±8.9 years) before endoprosthetic knee joint replacement, и 27 healthy individuals (55.6+8.3 years) who formed a control group. Total RNA was isolated from the blood and used to estimate the gene expression of mTOR, autophagy-related protein 1 (ATG1), the cyclin-dependent kinase inhibitor p21, caspase 3, and tumor necrosis factor-а (TNF-а) by real-time polymerase chain reaction. Results. Analysis of gene expression in the outpatients with OA identified two subgroups: in one subgroup (n = 13) mTOR expression was considerably much less than that in the control group; the expression of ATG1 and p21 did not differ greatly from the control and that of caspase 3 and TNF-α was significantly higher. The other outpatients (n = 20) and all the examined patients needing endoprosthetic replacement were ascertained to have a higher gene expression of mTOR, ATG1, p21, caspase 3, and TNF-α than in the control group. Before endoprosthetic replacement, severe joint destruction in patients with OA was associated with enhanced gene expression of mTOR, ATG1, p21, and caspase 3. Conclusion. In early-stage disease, increased mTOR gene expression may serve as a prognostic marker of the severity of the disease and articular cartilage destruction.