Adipose Mesenchymal Stem Cells Derived Exosomes Ameliorates KOA Cartilage Damage and Inflammation by Activation of PINK1-Mediated Mitochondrial Autophagy

Abstract

Knee osteoarthritis (KOA) is characterized by degenerative destruction of knee cartilage. Adipose tissue-derived mesenchymal stem cells (MSCs) have been widely used in the clinic to treat joint diseases, and the exosomes secreted by adipose tissue-derived MSCs (ADSC-Exos) are more stable and easier to store than stem cell therapy alone. The aim of this study was to investigate whether ADSC-Exos could reduce KOA chondrocyte damage and inflammation by activating mitochondrial autophagy. In vitro, we induced a KOA chondrocyte model with lipopolysaccharide (LPS), and after treatment with ADSC-Exos, we assessed chondrocyte damage and inflammation by using HE, Senna O solid green, and Alcian blue staining and IL-1β immunofluorescence analysis. We also labeled chondrocytes and assessed their intracellular levels of reactive oxygen species (ROS) using the DCFH-DA probe, assessed the mitochondrial membrane potential of chondrocytes using a mitochondrial membrane potential detection kit (JC-1). In vivo, we constructed a KOA rat model by anterior cruciate ligament tenotomy (ACLT) surgery, treated the knee joint with a local injection of ADSC-Exos, reconstructed the knee joint in three dimensions using micro-CT, and evaluated the pathological changes in cartilage tissues by using HE, Senna O solid green, and Alcian blue staining. The in vivo and in vitro results showed that ADSC-Exos upregulated the expression of PINK1/Parkin pathway components, promoted mitochondrial autophagy in chondrocytes, increased the mitochondrial membrane potential, protected mitochondrial function in chondrocytes, and ameliorated the degradation of the cartilage matrix and inflammation during KOA.

Keywords: PINK1/Parkin; adipose‐derived stem cells; exosome; knee osteoarthritis; mitophagy.