microRNA-129-5p shuttled by mesenchymal stem cell-derived extracellular vesicles alleviates intervertebral disc degeneration via blockade of LRG1-mediated p38 MAPK activation

Early human evidence such as case series or small samples is exploring possible benefits.

• 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)

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been reported to deliver exogenous microRNAs (miRNAs or miRs) to reduce the progression of intervertebral disc degeneration (IDD). The purpose of the current study was to investigate the therapeutic potential of MSC-derived EVs delivering miR-129-5p in IDD. First, miR-129-5p expression levels were quantified in nucleus pulposus (NP) tissues of IDD patients. An IL-1β-induced NP cell model with IDD was then established, and co-cultured with EVs derived from MSCs that had been transfected with miR-129-5p mimic or inhibitor to elucidate the effects of miR-129-5p on cell viability, apoptosis, and ECM degradation. In addition, RAW264.7 cells were treated with the conditioned medium (CM) of NP cells. Next, the expression patterns of polarization markers and those of inflammatory factors in macrophages were detected using flow cytometry and ELISA, respectively. Lastly, rat models of IDD were established to validate the in vitro findings. It was found that miR-129-5p was poorly-expressed in NP tissues following IDD. Delivery of miR-129-5p to NP cells by MSC-derived EVs brought about a decrease in NP cell apoptosis, ECM degradation and M1 polarization of macrophages. Moreover, miR-129-5p directly-targeted LRG1, which subsequently promoted the activation of p38 MAPK signaling pathway, thus polarizing macrophages toward

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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