Cytokines as Key Drivers of Pathological Root Resorption: Integrating Molecular Mechanisms, Genetic Determinants, and...

Cytokines are key regulators of immune responses and tissue remodeling, playing a central role in physiological homeostasis and pathological inflammation. Dysregulation of cytokine signaling networks has been implicated in a wide range of diseases, where persistent inflammatory activation leads to progressive tissue destruction and impaired repair mechanisms. In the oral environment, cytokines critically influence the balance between tissue resorption and regeneration, particularly in processes involving dentin and alveolar bone remodeling. Pathological root resorption (PRR) represents a clinically significant model of cytokine-driven tissue destruction, characterized by the loss of dental hard tissues mediated by osteoclast-like cells within a dysregulated inflammatory microenvironment. Although mechanical, infectious, and iatrogenic factors are well-established triggers, they alone do not fully explain the variability in clinical outcomes, suggesting an important role for host-related factors. New research highlights the relationship between inflammatory signaling pathways, genetic susceptibility, and molecular biomarkers in shaping the onset and progression of PRR. In particular, the RANK/RANKL/OPG axis, cytokine networks, and gene polymorphisms have been identified as key determinants of osteoclast activation and resorptive activity. At the same time, advances in salivary and gingival crevicular fluid biomarker research provide new opportunities for early detection and real-time monitoring. Despite these advances, current knowledge remains fragmented, with heterogeneous study designs, inconsistent genetic associations, and a lack of standardized diagnostic protocols, all of which limit clinical translation. Therefore, a comprehensive and integrative synthesis of cytokine-mediated mechanisms in PRR is needed. This review aims to provide an updated and critical overview of cytokine and chemokine involvement in PRR, integrating molecular pathways, genetic determinants, and emerging biomarkers within a unified framework while highlighting translational implications for precision dentistry.