Bone marrow mesenchymal stem cell-derived exosomes prevent osteoarthritis by regulating synovial macrophage polarization.

ABSTRACT

Osteoarthritis is a chronic degenerative disease that can lead to restricted activity or even disability. Bone marrow mesenchymal stem cells can repair cartilage damage and treat osteoarthritis via cell therapies or in-tissue engineering. Research has shown that the paracrine mechanism is the main mode of action of mesenchymal stem cells. Exosomes are the smallest known membrane-bound nanovesicles. Exosomes are also important carriers of paracrine delivery agents and promote communication between cells. We demonstrated that bone marrow mesenchymal stem cell-derived exosomes can delay the progression of osteoarthritis. Exosomes alleviate cartilage damage, reduce osteophyte formation and synovial macrophage infiltration, inhibit M1 macrophage production and promote M2 macrophage generation. In synovial fluid, the expression levels of the proinflammatory cytokines, IL-1ß, IL-6, and TNF-α were decreased and the release of the anti-inflammatory cytokine, IL-10 was increased. In vitro, macrophages treated with exosomes maintain chondrocytes' chondrogenic characteristics and inhibit hypertrophy. Our results demonstrated that bone marrow mesenchymal stem cell-derived exosomes may relieve osteoarthritis by promoting the phenotypic transformation of synovial macrophages from M1 to M2.