Roles of innate immune system and receptor Dectin-1 in synovium and cartilage homeostasis of osteoarthritis.

BACKGROUND

Innate immunity is crucial in the progression of osteoarthritis (OA); however, its mechanisms require further exploration. This study aims to investigate the mechanisms of innate immunity in OA synovitis.

METHODS

RNA sequencing data were analyzed to detect the expression characteristics of innate immunity-related genes in OA synovium. The Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database was used to identify hub genes, and an OA diagnostic model was constructed using 113 combinations of machine learning algorithms. Single-cell sequencing data were used to identify the expression patterns of hub genes and innate immunity-related pathways in cell clusters and to illustrate the interactions among cell populations. The functional mechanism of Dectin-1 in OA was validated experimentally.

RESULTS

Innate immunity-related genes and pathways were significantly expressed in the synovium of patients with OA. We constructed an OA diagnostic model, and HLA-DRA+ cells were identified as a critical cell population. The innate immune receptor Dectin-1 on macrophages regulated macrophage M1 polarization and cartilage homeostasis via the Dectin-1/Syk/NF-κB pathway, influencing the progression of OA.

CONCLUSION

This study reveals the expression patterns of innate immunity-related genes and pathways in the OA synovium and highlights the role of Dectin-1 in macrophages.