Exosomes from adipose-derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR-145 and miR-221

Osteoarthritis (OA) is one of the most prevalent joint disorders globally. Patients suffering from OA are often obese and adiposity is linked to chronic inflammation. In the present study, the potential of using exosomes isolated from adipose-derived stem cells (ADSCs) as a therapeutic tool for reducing chronic inflammation and promoting chondrogenesis was investigated using patient-derived primary cells. First, it was tested whether patient-derived ADSCs could differentiate into chondrogenic and osteogenic lineages. The ADSCs were then used as a source of exosomes. It was found that exosomes isolated from ADSCs, when co-cultured with activated synovial fibroblasts, downregulated the expression of pro-inflammatory markers interleukin (IL)-6, NF-kappa B and tumor necrosis factor-alpha, while they upregulated the expression of the anti-inflammatory cytokine IL-10; without exosomes, the opposite observations were made. In addition, inflammation-inflicted oxidative stress was induced in vitro by stimulating chondrocytes with H2O2. Treatment with exosomes protected articular chondrocytes from H2O2-induced apoptosis. Furthermore, exosome treatment promoted chondrogenesis in periosteal cells and increased chondrogenic markers, including Collagen type II and beta-catenin; inhibition of Wnt/beta-catenin, using the antagonist ICG-001, prevented exosome-induced chondrogenesis. Periosteal cells treated with exosomes exhibited higher levels of microRNA (miR)-145 and miR-221. The upregulation of miR-145 and miR-221 was associated with the enhanced proliferation of periosteal cells and chondrogenic potential, respectively. The present study provided evidence in support for the use of patient-derived exosomes, produced from ADSCs, for potential chondrogenic regeneration and subsequent amelioration of osteoarthritis.