CXCL12/CXCR4 Mediates Orthodontic Root Resorption via Regulating the M1/M2 Ratio

Area of Science:

• Biomedical Engineering
• Immunology
• Orthodontics

Background:

• External root resorption is a common side effect of orthodontic treatment.
• M1 macrophages are known to promote orthodontic root resorption (ORR).
• The precise mechanism linking mechanical force to the M1/M2 macrophage imbalance in periodontal tissue remains unclear.

Purpose of the Study:

• To elucidate the mechanism by which mechanical force stimulates the M1/M2 macrophage ratio in periodontal tissue.
• To investigate the role of the C-X-C motif chemokine 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis in force-induced ORR.
• To evaluate the therapeutic potential of blocking the CXCL12/CXCR4 axis.

Main Methods:

• Assessment of CXCL12+ periodontal ligament cells (PDLCs) and CXCR4+ monocytes in mice after force application and removal.
• In vitro analysis of CXCL12 expression in PDLCs under varying force conditions.
• Pharmacological blockade of the CXCL12/CXCR4 axis using AMD3100.
• Tracking of Ly6Chi inflammatory monocytes in lymph nodes and blood.
• Evaluation of macrophage polarization (M1/M2 ratio).

Main Results:

• Force application significantly increased CXCL12+ PDLCs and CXCR4+ monocytes, correlating with ORR.
• In vitro force stimulation dose-dependently increased CXCL12 expression in PDLCs.
• Blockade of the CXCL12/CXCR4 axis with AMD3100 alleviated ORR and normalized the M1/M2 macrophage ratio.
• The CXCL12/CXCR4 axis mediated the homing of Ly6Chi inflammatory monocytes and modulated macrophage polarization.

Conclusions:

• The force-induced CXCL12/CXCR4 axis is a key mediator of ORR.
• This axis promotes ORR by increasing the M1/M2 macrophage ratio via monocyte recruitment and polarization modulation.
• AMD3100 demonstrates potential as an inhibitor of orthodontic root resorption.