Exosomal miR-574-3p from adipose-derived mesenchymal stem modulates CRIM1/BMPs signaling to restrain chondrocytes hypertrophy and inflammatory response in knee osteoarthritis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Chondrocyte hypertrophy is an important feature of knee osteoarthritis (KOA) cartilage pathological damage, and existing evidence supports the potential therapeutic role of adipose-derived mesenchymal stem cells (ASCs) through exosomes. However, the differences of in exosome contents under different conditions and the mechanisms by which they affect the hypertrophic phenotype of chondrocytes remain unclear. Methods Exosomes from ASCs with or without the stimulation of IL-1β were extracted, identified by NTA, TEM, and membrane surface marker, stained with PKH26 to confirm the uptake by chondrocytes. Next, miRNA sequencing for these two types of exosomes were performed and miR-574-3p, significantly down-regulated in IL-1β stimulated ACSs exosomes, was identified the most distinct miRNAs. Besides, RNA-seq on chondrocytes, KOA chondrocytes, and KOA chondrocytes under the intervention of exosomes derived from ASCs were conducted, and intersected the obtained differentially expressed genes with potential target genes of miR-574-3p known from miRNA database. Further on, exosomal miR-574-3p From ACSs modulated cysteine-rich motor neuron protein 1 (CRIM1)/bone morphogenetic proteins (BMPs) signaling to restrain chondrocytes hypertrophy and inflammatory response in KOA were verified. Results Exosomal miR-574-3p from ASCs was significantly down-regulated under inflammatory stat

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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