Exosomes derived from mesenchymal stem cells rescue cartilage injury in osteoarthritis through Ferroptosis by GOT1/CCR2 expression

Abstract

Osteoarthritis is a prevalent joint disease that significantly affects the daily life of the elderly and is one of the primary causes of disability in this population. This study aims to evaluate the potential pro-inflammatory effects and molecular mechanism of Mesenchymal stem cells-derived exosomes (MSC-Exos) in Osteoarthritis. Bilateral ovariectomy was carried out to induce osteoporosis under anesthesia for the mice. MC3T3-E1 cells were induced for 14 days.HE staining, Safranin O staining and Biomechanical parameter analysis were used in this experiment. MSC-Exos improved osteoarthritis in a mouse model by reducing inflammation levels, preventing ferroptosis, and inducing expression of GOT1/CCR2 to regulate ferroptosis. MSC-Exos also promoted cell growth and osteogenic differentiation of bone cells in an in vitro model. Inhibition of GOT1 reduced the effects of MSC-Exos on cell growth and osteogenic differentiation in an osteoarthritis model. MSC-Exos induce Nrf2/HO-1 expression through the GOT1/CCR2 signaling pathway, resulting in the reduction of Ferroptosis. However, inhibition of Nrf2 reduces the effectiveness of MSC-Exos in treating Osteoarthritis.The results of this study suggest that the GOT1/CCR2/Nrf2/HO-1 signaling pathway plays a crucial role in MSC-Exos-mediated reduction of Ferroptosis in macrophages during Osteoarthritis. These findings may provide a potential therapeutic approach for Osteoarthritis and other orthopedic conditions.

Keywords: CCR2; Exosomes; GOT1; Mesenchymal stem cells; Osteoarthritis.