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

Root resorption is a pathologic 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.

This review provides a comprehensive analysis of the key signaling pathways and molecular mediators orchestrating root resorption in orthodontic, traumatic, and inflammatory conditions.

A literature-based analysis was conducted, focusing on molecular and cellular mechanisms involved in root resorption. Key pathways such as RANK/RANKL/OPG, Wnt signaling, ATP-P2RX7-IL-1, and inflammasome activation were examined. The role of proinflammatory and anti-inflammatory cytokines, matrix metalloproteinases, and periostin were also analyzed.

Proinflammatory mediators such as IL-1, IL-6, IL-8, tumor necrosis factor-alpha, IL-17, IL-22, and IL-23 drive odontoclastic differentiation, whereas anti-inflammatory cytokines, including IL-4, IL-10, and transforming growth factor-beta, 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.

The intricate cross talk between pro-resorptive and antiresorptive factors, emphasizing their roles in odontoclast activation and extracellular matrix remodeling, dictate the extent of root degradation.