Effects of dental pulp-derived mesenchymal stem cell exosomes produced under hypoxia conditions on osteoarthritic chondrocytes

PurposeOsteoarthritis is a common cause of disability worldwide. Exosomes are extracellular vesicles and can exert paracrine and endocrine actions. DPSCs exosomes offer a new avenue of research that may elucidate various functions related to cell proliferation, differentiation, and immunomodulation. We hypothesized that DPSC exosomes produced under hypoxia-induced culture conditions may have an anti-inflammatory effect on osteoarthritic chondrocytes and may re-regulate the inflammatory response that is increased in osteoarthritis. We also hypothesized that the decreased glycosaminoglycan production in osteoarthritis may be re-induced by DPSC exosomes produced under hypoxia. Materials and MethodsExosomes were isolated from DPSCs under hypoxic (3% O2) and normoxic conditions (21% O2) separately and were applied to OA chondrocyte cells. Quantification, morphology and analysis of tetraspanin markers were performed to characterize the exosomes. After the OA chondrocytes were treated with exosomes for 48 hours, they were prepared for cell proliferation, apoptosis, viability, glycosaminoglycan tests, and inflammatory cytokine analysis. ResultsOur results show that the pro-inflammatory cytokines were significantly suppressed in osteoarthritic chondrocytes by DPSC exosomes produced under hypoxia (p < 0.05). Exosomes of DPSCs grown in a hypoxia environment dramatically increase the amount of GAG in OA chondrocytes, giving clues that they can be used in cartilage regeneration (p < 0.001). ConclusionConsidering that OA is associated with inflammatory components, DPSC exosome produced under hypoxic conditions prevents the formation of proinflammatory cytokines in osteoarthritic chondrocytes and shows therapeutic effects on osteoarthritic chondrocytes. Our study provides the first evidence showing the efficacy of DPSC-derived exosomes produced under hypoxia on osteoarthritic chondrocytes.