Profiles of Exosomal microRNAs in Joint Cells and Candidate microRNAs for Cartilage Regeneration

The activation of chondrogenic progenitor cells (CPCs) in articular cartilage during a traumatic injury is vital for cartilage regeneration. Although our understanding of the mechanisms underlying CPC chondrogenic activation remains incomplete, there is evidence that exosomal microRNAs (miRNAs or miRs) are involved in tissue healing due to their regulating role of posttranscriptional gene expressions. In this study, we profiled enriched and differential expression of miRNAs in exosomes derived from bovine joint cells (CPCs, chondrocytes, and synoviocytes) via Next Generation Sequencing analysis and validated the potential therapeutic effects of candidate exosomal miRNAs for cartilage regeneration. For CPC-based cartilage regeneration, we tested the impact of administering miR-107, miR-140, and miR-148a on CPCs because we found that these miRNAs were highly and differentially expressed in chondrocytes-derived exosomes (CC-Exo). We found that: (1) miR-140 induced chondrogenic gene expression including SRY-box transcription factor 9, collagen type 2A1, and aggrecan, and (2) miR-107 suppressed catabolic gene expression including matrix metalloproteinase 3, a disintegrin and metalloproteinase with thrombospondin motifs 5, and nitric oxide synthase 2. Our findings indicate that transfection of CPCs with specific chondrogenic miRNAs present in CC-Exo have the potential to promote CPC-based cartilage regeneration and could be an important component of posttraumatic osteoarthritis prevention. Impact Statement Chondrocytes, chondrogenic progenitor cells (CPCs), and synoviocytes secrete exosomal microRNAs (miRNAs) that contribute to joint health and disease. These miRNAs could also have important implications for improving cartilage repair and regeneration. In this study, we identified candidate miRNAs that were enriched in chondrocytes-derived exosomes and found that these miRNAs induced chondrogenic gene expression or suppressed catabolic gene expression in a CPC monolayer culture system. These findings suggest that miRNA-based cartilage repair strategies could be developed to regenerate damaged and diseased cartilage.