Signaling Pathways in Root Resorption: Linking Inflammation, Odontoclastogenesis, and Tissue Remodeling.

Root resorption is a pathological process characterized by the breakdown of dentin and cementum by odontoclasts, mirroring the mechanisms of osteoclast-driven bone resorption. Osteoclastogenesis is tightly regulated by the RANK/RANKL/OPG axis and other signaling pathways, including Wnt, ATP-P2RX7-IL-1, programmed cell death, and inflammasome activation. Pro-inflammatory mediators such as IL-1, IL-6, IL-8, TNF-α, IL-17, IL-22, and IL-23 drive odontoclastic differentiation, whereas anti-inflammatory cytokines, including IL-4, IL-10, and TGF-β, counteract resorptive activity. Additionally, matrix metalloproteinases and periostin modulate extracellular matrix remodeling, impacting resorption progression. The balance between resorptive and reparative processes is influenced by the inflammatory microenvironment, fibroblast-macrophage interactions, and mechanotransduction. While the molecular mechanisms underlying odontoclastogenesis parallel bone resorption, unique features of root structures, such as the cementoid layer, contribute to resistance against resorption. This review provides a comprehensive analysis of the key signaling pathways and molecular mediators orchestrating root resorption in orthodontic, traumatic, and inflammatory conditions. It highlights the intricate crosstalk between pro-resorptive and anti-resorptive factors, emphasizing their roles in odontoclast activation, extracellular matrix remodeling, and the inflammatory microenvironment that dictates the extent of root degradation.