Selective loading of exosomal HULC and miR-372 is responsible for chondrocyte death during OA pathogenesis

Abstract

Exosomes are membranous vesicles containing various biomolecules, including non-coding RNAs (ncRNAs). ncRNAs are secreted from several cell types and are involved in various biological functions, including cellular communication. The aim of this study was to identify and illustrate the significance of the osteoarthritis (OA)-specific packaging of exosomal ncRNAs. In this study, we hypothesized that selective packaging of ncRNAs into exosomes would reflect the cellular response to chondrocyte death during OA pathogenesis. Exosomal HULC level significantly decreased in OA exosomes, whereas exosomal miR-372-3p level significantly increased in OA exosomes. In addition, chondrocytes with high HULC levels in the cytosol showed lower overall proliferation and higher apoptotic cell death than normal chondrocytes, whereas chondrocytes with high miR-372-3p in the cytosol showed higher overall proliferation and lower cell death than OA chondrocytes. Among the signaling molecules known to be involved in OA pathogenesis, GSK is one of the regulators of the selective exosomal packaging observed in OA chondrocytes. Inhibition of GSK observed in OA chondrocytes was responsible for enriched uploading of miR-372-3p and suppressed uploading of HULC during OA pathogenesis. In conclusion, we show that selective ncRNAs observed in OA play a critical role in chondrocyte proliferation/apoptosis.