How dog bone stem cell exosomes reduce joint inflammation

Abstract

Osteoarthritis is a degenerative disease of cartilage, and exosome derived from mesenchymal stem cells (MSCs) are considered promising for treating inflammatory musculoskeletal disorders, although their mechanisms are not fully understood. This study aimed to investigate the effects of exosomes derived from canine bone marrow mesenchymal stem cells (cBMSCs-Exos) on the expression of inflammatory factors and genes related cartilage matrix metabolism in IL-1β-induced canine chondrocytes. Canine BMSCs were isolated and characterized for surface markers and trilineage differentiation. Exosomes were then extracted and performed surface labeling detection. Canine chondrocytes were exposed to IL-1β to mimic osteoarthritis in vitro. Subsequently, the chondrocytes were treated with exosomes from BMSCs, and the expression levels of related genes and IL-6 protein were assessed. The mesenchymal stem cells isolated from bone marrow and cultured exhibited positive CD44 and CD90, negative expression of CD45 and HLA, and demonstrated potential to differentiate into adipocytes, osteoblasts and chondrocytes. Exosomes from BMSCs exhibited positivity expression of CD9, CD63 and CD81. Treatment with exosomes significantly reduced <i>IL-6</i> and <i>TNF-α</i> mRNA levels induced by IL-1β, as well as IL-6 protein expression. Additionally, a significant decrease was observed in the mRNA levels catabolic marker genes <i>MMP-13</i>, <i>ADAMTS-5</i>, and <i>COX2</i>. Conversely, there was a significant increase in the mRNA levels of anti-inflammatory cytokines <i>IL-4</i>, <i>IL-10</i>, and anabolic marker genes, such as <i>COL2A1</i>, <i>ACAN</i>, and <i>SOX9</i>. cBMSCs-Exos play a vital role in cartilage protection by suppressing the expression of pro-inflammatory and anabolic genes while simultaneously enhancing the expression of genes involved in synthesis metabolism.