FUNCTIONS OF THE mTOR SIGNALING PATHWAY IN NORMAL ARTICULAR CARTILAGE CHONDROCYTES AND IN OSTEOARTHRITIS

• Main Authors: E. V. Chetina, N. G. Kashevarova, E. P. Sharapova
• Format: Article
• Language: Russian
• Published: IMA-PRESS LLC 2016-12-01
• Series: Научно-практическая ревматология
• Subjects: mtor; osteoarthritis; articular cartilage; peripheral blood; regulation of metabolic pathways
• Online Access: https://rsp.mediar-press.net/rsp/article/view/2307
• ISSN: 1995-4484; 1995-4492

Osteoarthritis  (OA) is a chronic disease associated with pain, stiffness, limited mobility and joint inflammation, as well as articular cartilage destruction.  Recent studies have shown the importance  of chondrocyte  differentiation (hypertrophy) as one of the mechanisms  of cartilage degradation in OA. This suggests that chondrocyte  metabolism undergoes the profound changes during cartilage resorption,  which are due to dysregulation of cell function. One of the major cellular metabolic regulators is the protein mTOR (mechanistic target of rapamycin) that controls cell growth, proliferation, protein biosynthesis and integrates extracellular signals from growth factors and hormones with amino acid availability and intracellular energy status. The importance  of mTOR activity for articular cartilage destruction  in OAis confirmed by significant changes in the work of mTOR regulatory network that involves multiple intracellular (growth factors, adenosine triphosphate, oxygen availability, and autophagy) and extracellular (glucose, amino acids, lipids, and hexosamine) signals. Moreover, the altered expression of the mTOR gene in the blood of patients with OA is associated with either increased pain or synovitis, which indicates that there is a strong metabolic heterogeneity in patients with OA and a need for a differentiated therapeutic  approach. The above problems are discussed in this review.