Effect of Three Therapeutic Methods of Exercise, Ozone, and Stem Cells on the MEF2C Expression and Myostatin Levels in Femoral Muscle Tissue of the Osteoarthritis Rats

Aims: Myostatin and Myocyte Enhancer Factor 2C (MEF2C) are involved in muscle changes associated with bone problems. The aim of the present study was to determine the effect of three therapeutic methods of exercise, ozone, and stem cells on MEF-2C gene expression and myostatin levels of femoral muscle tissue in osteoarthritis rats. Methods & Materials: This experimental study was done on 63 male rats (mean age of 8-12 weeks and weight of 250-300 g). They were randomly divided into nine groups: the healthy control and osteoarthritis group and seven intervention groups of osteoarthritis rats, including , saline, exercise, ozone therapy, MSCs, MSCs+ozone therapy, exercise+ozone therapy, and exercise+MSCs. Osteoarthritis was induced in rats by surgery. The training program consisted of 30 min of running on a non-slip treadmill at a speed of 16 m/min. Rats in the MSCs group received 1×106 cells/kg. The ozone was injected into the articular line of the knee tibiofemoral at a concentration of 20 μg/mL. Tissue levels of myostatin were measured by enzyme-linked immunosorbent assay kits and MEF2C gene expression was measured by real-time polymerase chain reaction method.  Findings: Cell+exercise, exercise+ozone, and cell+ozone groups showed a significant increase in MEF2C gene expression and a significant decrease in myostatin levels compared with the cell, exercise, and ozone groups (P<0.05). In the exercise+cell group, these changes were greater. Conclusion: The results showed that the combination of exercise and MSCs with an increase in MEF2C gene expression and a decrease in myostatin levels, can possibly have beneficial effects on the stimulatory and inhibitory factors of interactions between muscle and bone in the osteoarthritis rats, and ultimately reduce the risks of muscle weakness due to osteoarthritis complications.