Combined therapies with exercise, ozone and mesenchymal stem cells improve the expression of HIF1 and SOX9 in the cartilage tissue of rats with knee osteoarthritis

Abstract

PurposeKnee osteoarthritis (OA) is a common type of degenerative joint disease which decreases the quality of life. Sex-determining region Y box 9 (SOX9) and hypoxia-inducible factor-1 (HIF1) are considered as the key regulators of OA. We investigated the effect of combined therapies with mesenchymal stem cells (MSCs), ozone (O3) and exercise training on SOX9 and HIF1 expression in the cartilage of rats with knee OA.MethodsKnee OA was induced by surgical method. OA rats were divided into model, MSCs, ozone, exercise, MSCs + ozone, MSCs + exercise, ozone + exercise and MSCs + ozone + exercise groups. Rats in the MSCs group received intraarticular injection of 1 × 106 cells/kg. Rats in the ozone group received O3 at the concentration of 20 μg/mL, once weekly for 3 weeks. Rats in the exercise group were trained on rodent treadmill three times per week. 48 hours after the programs, cartilage tissues were isolated and the expression of SOX9 and HIF1 was determined using Real-Time PCR.ResultsSignificant differences were found in the expression of SOX9 and HIF1 between groups (P < 0.0001). Although combined therapies with exercise, MSCs and O3 significantly increased the expression of SOX9 and HIF1 in the cartilage tissue of rats with knee OA, combination of exercise with O3 was significantly more effective compared to the other combined therapies (P < 0.001).ConclusionsCombined therapy with exercise, MSCs and O3 significantly increased the expression of SOX9 and HIF1 genes in the cartilage of rats with knee OA; however, exercise + O3 was significantly more effective.

The Effect of Aerobic Training and Ozone Therapy on the Levels of MFN1 and DRP1 Gene Expression in the Heart Tissue of Rats with Osteoarthritis

“…Simultaneous training and ozone therapy was also more effective than sole training and ozone therapy, in terms of reducing the levels of DRP1 and MFN1 gene expression in the heart tissue of rats with osteoarthritis. In line with the protective effect of exercise and ozone therapy, Asadi et al (21) reported that aerobic training and ozone therapy alone increased interleukin-10, as an anti-inflammatory cytokine, and decreased TNF-α in the cartilage tissue of rats with knee osteoarthritis. Therefore, it can be concluded that regular and aerobic exercise can improve joint disease by increasing joint metabolism, synovial fluid, as well as antioxidant and anti-inflammatory effects.…”

Exercise improves subchondral bone microenvironment through regulating bone-cartilage crosstalk

“…Moreover, the Sox9 gene has been found to play a crucial role in this process, which suggests its importance in stress transmission and response ( 132 ). At present, there are many kinds of exercise interventions in animal studies related to exercise-mediated Sox9 treatment of osteoarthritis, for example, treadmill running, Combined therapies with exercise, ozone, and mesenchymal stem cells ( 133 ), vibration exercise with different frequencies ( 134 ).…”

Efecto de la aplicación intrauterina de ozono sobre la migración de neutrófilos y la endometritis subclínica en ganado lechero

“…Se ha reportado que el tratamiento con ozono fue efectivo para disminuir la severidad de la enfermedad inflamatoria pélvica en un modelo de ratas; efecto presuntamente asociado a la disminución en la expresión de los factores inflamatorios IL-6 y TNF-α (28) . En otro estudio, se reportó que pacientes con osteoartritis que recibieron tratamiento local con ozono tuvieron mayor expresión de IL-10 (factor antiinflamatorio) y menores niveles de TNF-α (29) . Con base en esto, es posible que, con el protocolo utilizado, la terapia de ozono haya disminuido la respuesta inflamatoria local en vacas con antecedentes de metritis.…”

“…Estos resultados sugieren que la terapia con ozono utilizada pudiera tener también un efecto antiinflamatorio en el endometrio. Además, con base en otros estudios (28,29) , el mecanismo pudiera ser a través de la modulación a la baja de la expresión de factores inflamatorios en vacas con antecedentes de metritis, hipótesis pendiente de ser desafiada.…”