Lutein Attenuates Synovial Hyperplasia, Cartilage Loss, and Bone Erosion by Suppressing Inflammatory Pathways in...

Lutein is a bioactive carotenoid best known for its role in retinal protection, but emerging evidence suggests that it may also exert anti-inflammatory activity in chronic inflammatory disorders. In this study, we investigated the anti-inflammatory and joint-protective effects of lutein in rheumatoid arthritis (RA)-related experimental models. Transcriptomic profiling was performed in MH7A fibroblast-like synovial cells treated with lutein, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). The results showed that lutein regulated inflammation-related transcriptional programs, particularly pathways associated with cytokine signaling and inflammatory responses. In TNF-α-activated MH7A cells, lutein suppressed inflammatory cytokine production and inhibited cell proliferation. The in vivo effects of lutein were further evaluated in a collagen antibody-induced arthritis (CAIA) mouse model. Mice were assigned to control, CAIA, and lutein-treated CAIA groups, and disease progression was assessed by monitoring body weight, paw thickness, and arthritis scores. Lutein treatment significantly attenuated arthritis severity and joint inflammation without affecting body weight. Micro-computed tomography demonstrated reduced bone erosion and osteophyte formation in lutein-treated CAIA mice. Histological analyses using hematoxylin and eosin and Safranin O staining further showed that lutein alleviated synovial hyperplasia and cartilage destruction. These findings indicate that lutein exerts anti-inflammatory and joint-protective effects in experimental models relevant to RA and support further mechanistic and preclinical investigation of lutein as a bioactive natural compound in inflammatory joint disease.