International journal of biological macromolecules · 2025
Roles of innate immune system and receptor Dectin-1 in synovium and cartilage homeostasis of osteoarthritis.
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Wu Han, Qian Yewen, Zhu Kaiyuan, Deng Zengfa, Zeng Hua, Li Jintao, Li Haosheng, Liao Guoqing, Chen Lingxiang, Que Yonghua, Huang Weisen, Wang Hechong, Fang Hang, Huang Guangxin, Hu Shu
Аннотация
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.
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.