Comparing the Effects of Regular Aerobic Training, Hyaluronic Acid, and Mesenchymal Stem Cells on Wnt/β-Catenin Signaling of Cardiac Tissue in Rats with the Experimental Model of Knee Osteoarthritis

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Abstract
Background: The present study aimed to compare the effects of three therapeutic methods, including regular aerobic training, hyaluronic acid (HA), and mesenchymal stem cells, on Wnt/β-catenin signaling of cardiac tissue in rats with the experimental model of knee osteoarthritis. Methods: Sixty-three male rats were divided into nine groups (seven in each group): (1) healthy control, (2) patient control, (3) sham, (4) saline, (5) exercise (EXT), (6) mesenchymal stem cells (MSCs), (7) hyaluronic acid, (8) EXT + MSCs, and (9) EXT + HA. After inducing the osteoarthritis (OA) model, we conducted 5 days of running on the treadmill for five weeks for the EXT group. Also, HA was injected intra-articularly. After 12 to 14 hours of fasting and 72 hours following the last training session, we conducted cardiac tissue sampling for β-catenin, GSK-3β, Wnt, Fz, TCF, and DKK1 analysis. We used RT-PCR to analyze the expression of the β-catenin, GSK-3β, Wnt, Fz, TCF, and DKK1 genes in cardiac tissue. The data were analyzed using one-way ANOVA and Tukey's post hoc test (P < 0.05). Results: Osteoarthritis induction significantly decreased the expression of the GSK-3β and DKK1 genes but significantly increased the expression of the β-catenin, Wnt, Fz, and TCF genes of cardiac tissue compared to the control group. However, the EXT, HA, MSC, and combination methods increased the expression of the GSK-3β and DKK1 genes but decreased the expression of the β-catenin, Wnt, Fz, and TCF genes of cardiac tissue, which were significant in the combination group. Conclusions: Regular exercise, along with HA and MSCs, may have protective effects for the following reasons: (1) reducing the expression of the β-catenin, Wnt, Fz, and TCF genes; (2) increasing the expression of the GSK-3β and DKK1 genes in cardiac tissue; and (3) inhibiting Wnt signaling in the heart.

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