Bone Mesenchymal Stem Cell-Derived Extracellular Vesicles Containing Long Noncoding RNA NEAT1 Relieve Osteoarthritis.

Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (BMSCs) possess potentials in modulation of the biological process in various diseases. However, an extensive investigation of the mechanism of BMSC-derived EVs (BMSC-EVs) in osteoarthritis (OA) remains unknown. Thus, we focused on the mechanism behind BMSC-EVs in OA. Cartilage tissues were harvested from OA patients, in which the microRNA (miR)-122-5p and Sesn2 expression were determined. BMSCs and their EVs were extracted. Chondrocytes were cocultured with BMSC-EVs overexpressing NEAT1, followed by gain- or loss-of-function assays for studying their effect on cell proliferation, apoptosis, and autophagy. Relationship among NEAT1, miR-122-5p, and Sesn2 was assessed. OA mouse model was established by the destabilization of medial meniscus method to elucidate the effect of NEAT1 in vivo. NEAT1 could be transferred from BMSC-EVs into the chondrocytes. miR-122-5p was highly expressed but Sesn2 was poorly expressed in cartilage tissues of OA patients. Mechanically, NEAT1 bound to miR-122-5p to limit miR-122-5p expression which targeted Sesn2, thus activating the Nrf2 pathway. In chondrocytes, NEAT1 delivered by BMSC-EVs, miR-122-5p downregulation, or Sesn2 overexpression induced the proliferation and autophagy of chondrocytes but inhibited their apoptosis. Meanwhile, NEAT1 delivered by BMSC-EVs relieved OA by regulating the miR-122-5p/Sesn2/Nrf2 axis in vivo. Taken altogether, BMSC-EVs containing NEAT1 activated the Sesn2/Nrf2 axis via binding to miR-122-5p for protection against OA.