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Regulatory Mechanism of ERKs Pathway on Orthodontic Force Signal Transduction and Osteogenic Differentiation
Ziliang Yang1,2, Sihui Hu3, Xinyi Li4
1Department of Orthodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration.
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.
Insights
The extracellular signal-regulated kinases (ERKs) pathway drives orthodontic tooth movement and bone remodeling, partly via STAT3. Targeting the ERKs/STAT3 axis may accelerate orthodontic treatment.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Orthodontics
Background:
- Orthodontic tooth movement (OTM) involves complex mechanotransduction processes.
- The role of the extracellular signal-regulated kinases (ERKs) pathway and its interaction with signal transducer and activator of transcription 3 (STAT3) in OTM is not fully understood.
Purpose of the Study:
- To investigate the ERKs signaling pathway's role in orthodontic force-induced mechanotransduction and osteogenic differentiation.
- To explore the crosstalk between ERKs and STAT3 in the context of OTM.
Main Methods:
- In vitro: MC3T3-E1 cells subjected to cyclic tensile strain with or without an ERKs inhibitor (SCH772984).
- In vivo: Mouse OTM model treated with SCH772984; analysis of pathway proteins, osteogenic markers, tooth movement, and bone microarchitecture.
Main Results:
- Mechanical strain activated ERKs and STAT3 phosphorylation, upregulating osteogenic markers in vitro, effects inhibited by SCH772984.
- In vivo, orthodontic force induced bone remodeling and OTM; SCH772984 suppressed ERKs activation and reduced tooth movement by approximately 40%.
Conclusions:
- The ERKs pathway is crucial for orthodontic force-induced alveolar bone remodeling and OTM, partially mediated through STAT3.
- The ERKs/STAT3 axis represents a potential therapeutic target for accelerating orthodontic treatments.
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