Background: Currently, a large number of molecular biological and genetic markers are known to be involved in the development of osteoarthritis (OA). The mammalian target of rapamycin (mTOR) signaling pathway is responsible for chondrocyte proliferation, cartilage matrix production, and cell growth. OA is characterized by increased mTOR synthesis, which is accompanied by an increase in proliferative activity and destruction of chondrocytes. Obesity is an important factor in the progression of knee OA. The study of mTOR expression in patients with OA and obesity is an urgent task in the development of personalized OA therapy.
Objectives: To determine the expression of mTOR in patients with knee OA in combination with obesity and normal body weight. To evaluate the effect of mTOR on the clinical manifestations of OA in patients with different body mass index (BMI).
Methods: The study included 73 female patients aged 45-65 y.o. with Kellgren-Lawrence stage II-III knee OA. The patients were divided into 2 groups: group 1 (n=50) with obesity (BMI > 30 kg / cm2) and group 2 (n=23) with normal or increased body weight (BMI < 30 kg/cm2). The average age of patients with obesity is 56.5 ± 5.87 years, without obesity - 58.7 ± 5.43 years. Clinical manifestations were evaluated by a WOMAС. RNA was isolated from the patients ‘ blood samples, which was used to determine the expression of mTOR.
Results: Patients with knee OA with and without obesity did not differ in age. OA develops at an earlier age in obese patients, than in non-obese patients (p < 0.001). Patients from 1 group had a high BMI > 30 kg/m2 at the onset of OA. Obese patients had more severe knee OA is significantly more often detected: Kellgren-Lawrence stage III was determined in 10% of obese patients and in 4.35% - without obesity (p < 0.001). Significantly higher values of the WOMAC index pain, stiffness, joint functional failure, and total WOMAC were observed in obese patients (p = 0.006, p = 0.039, p = 0.037, and p = 0.014, respectively). Obese patients had higher VAS pain scores (p < 0.05) compared to patients with a lower BMI. Obese patients had a higher mTOR expression (p < 0.05) of 8.02±8.62, compared to non-obese patients. High mTOR expression was associated with VAS knee pain (r=0.78; p < 0.05) and WOMAC pain (r=0.89; p<0.05) in obese patients (Table 1).
Conclusion: Our study showed that patients with obesity and knee OA have higher rates of mTOR expression, compared to patients with normal body weight. High mTOR expression correlates with the severity of knee pain in obese patients. Thus, the evaluation of mTOR expression in obese patients and knee OA plays an important role in predicting the severity of clinical manifestations of OA, and may influence the choice of personalized therapy tactics for such patients.
Disclosure of Interests: None declared
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