Cellular and Molecular Neuro-Bone Cell Interactions Drive Alveolar Bone Remodeling During Orthodontic Mechanical Loading

作者：Xinyi Fang, Chi Liao, Jiamin Wan, Chunmiao Jiang, Yating Yi, Jun Wang, Qianming Chen, Jiu Lin, Xiaoyan Chen · 发表于：International Journal of Biological Sciences · 年份：2026 · DOI：10.7150/ijbs.129449 · 被引用次数：6 · 研究领域：Orthodontics and Dentofacial Orthopedics、dental development and anomalies、Bone Metabolism and Diseases

Orthodontic tooth movement (OTM) is a biomechanically driven process governed by dynamic cellular and molecular signaling interactions between neural and skeletal systems. This review synthesizes current evidence on neuron-bone cell crosstalk and the coordinated involvement of immune and vascular components in regulating alveolar bone remodeling during OTM. Key neural contributors include sensory neurons (nociceptors), autonomic neurons, central nervous system (CNS) circuits, and Schwann cells, which communicate with osteoblasts, osteoclasts, and periodontal ligament cells to modulate their proliferation, differentiation, and functional activity. These interactions are mediated by defined signaling pathways, including neuropeptide signaling (CGRP-CLR, SP-NK1, NGF-TrkA, BDNF-TrkB), axon guidance signaling (Sema3A-PlexinA/Nrp1), adrenergic signaling (β2-AR-dependent pathways), and intracellular cascades such as Rac1-β-catenin, RhoA/ROCK2, and Notch3. Sensory nerves function as primary initiators by releasing neuropeptides that promote osteoclastogenesis in pressure zones and osteogenesis in tension zones, while simultaneously shaping local immune responses and vascular remodeling. The autonomic nervous system exerts context-dependent regulation, with sympathetic signaling favoring bone resorption and parasympathetic pathways emerging as modulators of osteogenesis and neurovascular homeostasis. CNS circuits integrate sensory and autonomic inputs to coordinate OTM kinetics and pa...