NMN-primed exosomes derived from infrapatellar fat pad mesenchymal stem cells exert synergistic anti-inflammatory and cartilage-protective effects via MERTK pathway activation 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)

Osteoarthritis (OA) is a chronic degenerative joint disease lacking effective disease-modifying therapies. This study evaluated the therapeutic potential of nicotinamide mononucleotide (NMN)-primed exosomes derived from infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs), termed Exo NMN(+) , under the hypothesis that NMN priming enhances their anti-inflammatory, antioxidant, and chondroprotective efficacy through MERTK-dependent signaling. Exo NMN(+) were isolated and characterized by nanoparticle tracking analysis and Western blotting, showing enrichment of exosomal markers (CD9, CD63, ALIX) without size alteration, indicating enhanced cargo loading. In IL-1β-stimulated human chondrocytes, Exo NMN(+) improved viability, migration, and proliferation (increased Ki-67 and EdU expression), suppressed catabolic factors (MMP2, MMP9, VEGF), and upregulated anabolic markers (COL2A1, MERTK). Transcriptomic profiling identified 428 uniquely regulated genes, primarily involved in PI3K-AKT and small-GTPase signaling. Intersection analysis with single-cell OA datasets revealed five shared differentially expressed genes forming the basis of the GAS6-MERTK-PI3K/AKT axis. Exo NMN(+) also reduced intracellular reactive oxygen species (by 51 %) and apoptosis (by 60 %), effects abrogated upon MERTK knockdown, confirming pathway specificity. In a papain-induced OA mouse model, intra-articula

Evidence level

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

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