Ameliorative Effects of Bone Marrow-derived Mesenchymal Stem Cells and Hyaluronic Acid on Monosodium Iodoacetate-Induced Ankle Osteoarthritis in Wistar Rats: Roles of Th1/Th2/Th17 cytokines, MMP-13, TGF-β1 and antioxidant defense system

Abstract Background: There is currently no cure for osteoarthritis [OA], and the few pharmacological therapy options available have drawbacks. Additionally, there is no effective treatment that would guarantee a full recovery from OA. Therefore, the goal of this investigation was to determine if bone marrow mesenchymal stem cells [BMMSCs] and/or hyaluronic acid [HA] were effective in treating experimentally-induced ankle osteoarthritis in Wistar rats caused by monosodium iodoacetate [MIA]. Methods : In five groups of ten rats each, fifty male Wistar rats were distributed. Saline was injected into the right tibiotarsal joint of individuals in group I on two days in a row, whereas those in group II received an injection of 2 mg of MIA [dissolved in saline] into the same joint. Those in groups III [MIA-BMMSCs], IV [MIA-HA], and V [MIA-BMMSCs+HA] were injected with MIA similarly to those in group II and also received intra-articular injections of BMMSCs [1×10 6 cells/rat], HA [75 µg/rat], and BMMSCs [1×10 6 cells/rat] alongside HA [75 µg/rat] respectively, in the tibiotarsal joint at the ends of the 2 nd , 3 rd and 4 th weeks after MIA injection. The leg circumference, arthritis score, and morphological changes of the ankle joint were evaluated weekly from the beginning to the end of the experiment. For the purpose of identifying oxidative stress, antioxidant, and inflammatory state indicators, sera were collected. For histological and molecular research, the ankles of the right hind leg were excised out and fixed in neutral buffered formalin. Results: In addition to raising GSH and GST levels, BMMSCs and HA decreased serum LPO. Additionally, BMMSC and HA significantly decreased ankle MMP-13 mRNA and TGF-β1 protein expressions as well as TNF-α and IL-17 serum levels. Rats with MIA-induced OA had higher serum IL-4 levels after receiving BMMSC and HA. BMMSC and HA caused a steady decrease in joint injury and cartilage degradation, according to histological investigations. Conclusion: Based on the findings, it is possible to infer that BMMSC and/or HA have anti-arthritic effects that may be mediated by the augmentation of the antioxidant and anti-inflammatory effects in Wistar rats with MIA-induced osteoarthritis. The suppression of MMP-13 and TGF-β1 expressions play an important role in the improvement effects BMMSC and/or HA on OA in Wistar rats.