Immuno-metabolic crosstalk in osteoarthritis: from mechanisms to therapies

Abstract

Osteoarthritis (OA) is a heterogeneous whole-joint disorder influenced by mechanical stress, aging, previous trauma, genetic susceptibility, subchonrral bone alterations, and localized inflamation.Emerging evidence suggests that immune and metabolic processes alterations may be involved in OA pathogenesis particularly in inflammatory and metabolically dysregulated subtypes. This narrative review summarizes the bidirectional crosstalk between immune and metabolic processes during OA progression. Human observational studies and experimental models suggest that immune-cell activation and metabolic dysfunction may interact to influence synovial inflammation and cartilage homeostasis although their causal relevance and relative contributions vary across OA phenotypes. We further discuss emerging immunometabolic strategies targeting glycolytic and lipid-metabolic pathways as well as predominantly experimental approaches involving gene editing synthetic biology and stem cell-based therapies. Integrating multi-omics technologies with personalized medicine may improve patient stratification and dynamic monitoring and could facilitate the future development of more personalized and potentially disease-modifying strategies for OA.Future research should focus on clarifying the dynamic immunometabolic network underlying OA and promoting the clinical translation of innovative strategies through artificial intelligence and interdisciplinary collaboration.