BMSC-derived Exosomes Attenuate Rat Osteoarthritis by Regulating Macrophage Polarization, and PINK1/Parkin Signaling May Be Involved

Abstract

Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may modulate the M1/M2 polarization of macrophages during osteoarthritis (OA). However, the underlying mechanisms of BMSC-Exos in this process still need to be elucidated. In this study, the effects of BMSC-Exos on macrophages after induction of lipopolysaccharide (LPS) were determined. The protein expression of Akt, PINK1, and Parkin in macrophages were tested. We prepared an OA model by resecting the anterior cruciate ligament and medial meniscus of SD rats. BMSC-Exos could reduce M1 and promote M2 macrophage polarization, inhibit mitochondrial membrane damage and reactive oxygen species (ROS) production. Akt phosphorylation was downregulated but significantly recovered after treatment with BMSC-Exos (P<0.01). PINK1/Parkin signaling was crucial in mitochondrial damage and subsequent M1 macrophage polarization. The protein expression of PINK1 and Parkin was significantly inhibited by BMSC-Exos (P<0.01). Histological analyses revealed that BMSC-Exos alleviated cartilage damage, inhibited M1 polarization, and promoted M2 polarization in the synovium. The expression of PINK1 and Parkin in the synovium was decreased when BMSC-Exos were used. ELISA results revealed that BMSC-Exos also changed the systematic inflammatory state. These data suggest that BMSC-Exos ameliorate OA development by regulating synovial macrophage polarization, and one of the underlying mechanisms may be through inhibiting PINK1/Parkin signaling. Therefore, BMSC-Exos are a potential useful therapeutic approach for OA.