Regulatory Mechanism of ERKs Pathway on Orthodontic Force Signal Transduction and Osteogenic Differentiation.

OBJECTIVES

This study aimed to investigate the role of the extracellular signal-regulated kinases (ERKs) signaling pathway in orthodontic force-induced mechanotransduction and osteogenic differentiation, and explore its potential crosstalk with signal transducer and activator of transcription 3 (STAT3), whose regulatory mechanism remains unclear.

MATERIALS AND

METHODS

In vitro, MC3T3-E1 preosteoblasts were exposed to cyclic tensile strain (2000 μstrain, 0.5 Hz, 4 h) with or without the specific ERKs inhibitor SCH772984. In vivo, a mouse orthodontic tooth movement (OTM) model was established with 4g force, and SCH772984 was locally injected into periodontal tissues. Pathway protein expression, osteogenic marker levels, tooth movement distance, and bone microarchitecture were analyzed.

RESULTS

Mechanical strain significantly activated ERKs and STAT3 phosphorylation and upregulated key osteogenic markers (Runx2, OSX, OPN, ALP) in vitro; these effects were inhibited by SCH772984 except for COL1. In vivo, orthodontic force-induced alveolar bone remodeling and OTM, with osteogenic markers predominantly elevated on the tension side. SCH772984 treatment suppressed ERKs activation and reduced tooth movement by ~40% (all P<0.05).

CONCLUSIONS

The ERKs pathway is a critical mediator of orthodontic force-induced alveolar bone remodeling and OTM, functioning partially through STAT3. These findings establish the ERKs/STAT3 axis as a promising therapeutic target for accelerating orthodontic treatment.