Bone marrow mesenchymal stem cell exosome-derived miR-223 regulated cellular pyroptosis of macrophage in osteomyelitis through regulating LACC1.

Osteomyelitis (OM) is a severe bone infection characterized by inflammation and tissue damage. Macrophages play a crucial role in the inflammatory response during OM, and exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been proposed as potential therapeutic agents. Previous studies suggest that miR-223, a microRNA involved in inflammatory processes, is dysregulated in OM. This study investigates the role of BMSCs-derived exosomes carrying miR-223 in regulating macrophage pyroptosis, a form of programmed cell death triggered by inflammation. Blood samples were collected from OM patients and control subjects to assess miR-223 expression. BMSCs were treated with LPS to simulate the OM environment. Exosomes were extracted from miR-223 overexpressing BMSCs and characterized. The effects of these exosomes on macrophage survival, apoptosis, and pyroptosis were assessed through CCK-8 assays, flow cytometry, TUNEL staining, ELISA, and western blotting. The miR-223-mediated regulation of Caspase-1 and LACC1 expression was evaluated using specific inhibitors and gene expression analysis. miR-223 expression was significantly reduced in OM patients and in LPS-treated BMSCs. BMSCs-derived exosomes carrying miR-223 (miR-223 exo) enhanced macrophage viability, reduced apoptosis, and mitigated LPS-induced pyroptosis by targeting the NLRP3 inflammasome and Caspase-1 expression. Co-treatment with miR-223 inhibitors and Caspase-1 inhibitors showed that miR-223 regulated macrophage survival and inflammation through Caspase-1 modulation. Further investigation revealed that miR-223 targeted LACC1 to alleviate macrophage pyroptosis, with LACC1 overexpression reversing the protective effects of miR-223. BMSCs-derived exosomes carrying miR-223 play a protective role in OM by regulating macrophage pyroptosis and inflammation. This effect is mediated through the modulation of Caspase-1 and LACC1 expression, highlighting the potential of miR-223-based therapies for OM treatment.