TY  - EJOU
AU  - Ricciardi, Gabriele 
AU  - Ballato, Mariagiovanna 
AU  - Carlo, Gabriele Di 
AU  - Donadio, Domenico 
AU  - Germanà, Emanuela 
AU  - Corpina, Flavio 
AU  - Lipari, Carmela 
AU  - Fadda, Guido 
AU  - Leonetti, Danilo 
AU  - Zampogna, Biagio 
AU  - Ferlazzo, Marco 
AU  - Martini, Maurizio 

TI  - The role of leptin in osteoarthritis: from pathogenesis to clinical implications
T2  - European Cytokine Network

PY  - 
VL  - 
IS  - 
SN  - 1952-4005

AB  - Osteoarthritis (OA) is increasingly recognized as a multifactorial disease in which metabolic dysfunction and chronic low-grade inflammation contribute to joint degeneration. Among the mediators involved, leptin has emerged as a key adipokine linking obesity, aging, and inflammatory processes to OA development and progression. However, despite growing evidence, its role remains incompletely understood, and a comprehensive framework integrating leptin-related mechanisms across different joint tissues is still lacking. This review provides an updated overview of the role of leptin in OA pathogenesis, focusing on its effects on cartilage, synovium, subchondral bone, and the infrapatellar fat pad. We also discuss the interplay between leptin, obesity, inflammaging, and cellular senescence, together with its potential utility as a biomarker and therapeutic target. Current evidence indicates that leptin promotes inflammation, extracellular matrix degradation, pain sensitization, and tissue remodeling through multiple signaling pathways. Elevated leptin levels have been associated with disease severity and metabolically driven OA phenotypes, supporting its role as a molecular link between systemic metabolic alterations and local joint pathology. Nevertheless, important questions remain regarding its context-dependent effects and clinical applicability. A better understanding of leptin-related mechanisms may improve patient stratification and support the development of precision medicine approaches for inflammatory–metabolic OA phenotypes.
KW  - Osteoarthritis; leptin; adipokines; inflammaging; metabolic phenotype; joint degeneration

DO  - 10.32604/ecn.2026.084855