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RANKL+ senescent cells under mechanical stress: a therapeutic target for orthodontic root resorption using senolytics
Yue Zhou1, Aki Nishiura2, Hidetoshi Morikuni1
1Department of Orthodontics, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata, Osaka, Japan.
International Journal of Oral Science
|May 30, 2023
Summary
Mechanical stress during orthodontic tooth movement causes cellular senescence, leading to root resorption. Senolytics, like dasatinib and quercetin, effectively prevented this by targeting senescent cells and reducing root resorption.
Area of Science:
- Dentistry
- Cellular Biology
- Orthodontics
Background:
- Orthodontic root resorption is a common complication with no effective treatments.
- The role of cellular senescence in this process is not well understood.
Purpose of the Study:
- To investigate the role of senescent cells in orthodontic root resorption.
- To evaluate the efficacy of senolytics in preventing this complication.
Main Methods:
- An orthodontic intrusion tooth movement model in rats was used.
- Cellular senescence was identified using p21 and p16 markers.
- Receptor activator of nuclear factor-kappa B (RANKL) expression was analyzed.
- Senolytics (dasatinib and quercetin) were administered orally.
Main Results:
- Mechanical stress induced cellular senescence in cementoblasts and periodontal ligament cells.
- Senescent cells expressed RANKL, promoting odontoclast formation and root resorption.
- Senolytics significantly reduced senescent cells and alleviated root resorption.
- Evidence of senescent odontoclasts was observed in resorption fossae.
Conclusions:
- Aberrant stimuli in orthodontic intrusive tooth movement induce RANKL-expressing senescent cells.
- These senescent cells play a critical role in odontoclastogenesis and root resorption.
- Targeting senescent cells with senolytics offers a potential therapeutic strategy to prevent orthodontic root resorption.
