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

Abstract

Introduction: 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.

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

Methods: 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.

Results: 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.

Conclusion: 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.