Open Access

REVIEW

The role of leptin in osteoarthritis: from pathogenesis to clinical implications

Gabriele Ricciardi^1,2,#,*, Mariagiovanna Ballato^1,#, Gabriele Di Carlo³, Domenico Donadio^1,2,4,5, Emanuela Germanà¹, Flavio Corpina^2,6,7, Carmela Lipari^2,6,8, Guido Fadda⁹, Danilo Leonetti³, Biagio Zampogna^3,4,5, Marco Ferlazzo², Maurizio Martini^9,*

1 BIOMORF Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, A.O.U. Policlinico “G.Martino”, University of Messina, Via Consolare Valeria 1, Messina, Italy
2 Istituto Clinico Polispecialistico C.O.T. Cure Ortopediche Traumatologiche s.p.a., Messina, Italy
3 BIOMORF Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, Section of Orthopaedic and Trauma Surgery, A.O.U. Policlinico “G.Martino”, University of Messina, Via Consolare Valeria 1, Messina, Italy
4 Operative Research Unit of Orthopaedic and Trauma Surgery, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, Rome, Italy
5 Research Unit of Orthopaedic and Trauma Surgery, Department of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Via Alvaro del Portillo 21, Rome, Italy
6 Foresight Consulting, Messina, Italy
7 Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Messina, Italy
8 Research Unit of Artificial Intelligence and Computer Systems, Department of Engineering, Università Campus Bio-Medico di Roma, Rome, Italy
9 Department of Human Pathology of Adults and Developmental Age “Gaetano Barresi,” Division of Pathology, University of Messina, Messina, Italy

* Corresponding Authors: Gabriele Ricciardi. Email: ; Maurizio Martini. Email:
# These authors contributed equally to this work

European Cytokine Network 2026, 37(3), 169-191. https://doi.org/10.32604/ecn.2026.084855

Received 30 April 2026; Accepted 25 August 2026; Issue published 28 September 2026

Abstract

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.

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Keywords

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Supplementary Material

Supplementary Material File

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