Targeted Inhibition of CD74⁺ Macrophages by Luteolin via CEBPB/P65 Signaling Ameliorates Osteoarthritis Progression.

ABSTRACT: Synovial inflammation represents a hallmark pathological process in osteoarthritis (OA), yet the cellular drivers orchestrating this response remain incompletely defined. Through single-cell transcriptomic profiling of human OA synovial tissues, a distinct subset of CD74⁺ macrophages is identified that displayed robust pro-inflammatory transcriptional signatures, underscoring the pivotal role of macrophages in shaping the inflammatory microenvironment. To explore therapeutic opportunities, computational ligand-target interaction analysis predicted luteolin as a high-affinity binder of CD74. Mechanistically, luteolin suppressed CD74 expression and disrupted the assembly of the CEBPB-p65 complex, thereby preventing p65 nuclear translocation and subsequent activation of the NF-κB signaling ca

SUBMITTER: Peng R 

PROVIDER: S-EPMC12866766 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature