Discoidin Domain Receptor 2 Is Required for Tooth Extraction Socket Healing

Area of Science:

• Biochemistry
• Cell Biology
• Regenerative Medicine

Background:

• Discoidin Domain Receptor 2 (DDR2) is a tyrosine kinase vital for bone development and regeneration.
• DDR2's role in alveolar bone healing remained unexplored despite its expression in this tissue.

Purpose of the Study:

• To investigate the function of DDR2 in alveolar bone formation during tooth socket healing.
• To determine the cellular contribution of DDR2-expressing cells to socket repair.

Main Methods:

• Utilized global and conditional knockout mouse models (Ddr2LacZ/LacZ, Gli1CreERT2; Ddr2fl/fl) and lineage tracing (Ddr2mer-cre-mer; R26RtdTomato, Gli1CreERT2; R26RtdTomato).
• Analyzed tooth socket healing post-extraction through histological assessments, cell proliferation assays, apoptosis detection, and collagen fibril orientation analysis.

Main Results:

• Global Ddr2 deficiency significantly impaired socket healing, marked by reduced cell proliferation and disrupted collagen organization.
• Lineage tracing revealed that both DDR2+ and GLI1+ cells contribute to socket healing, with DDR2 likely functioning within GLI1+ skeletal progenitor cells.
• Conditional knockout of Ddr2 in Gli1+ cells partially inhibited socket repair, confirming DDR2's role in these progenitor cells.

Conclusions:

• DDR2 plays a significant role in alveolar bone repair following tooth extraction.
• DDR2's function in GLI1+ progenitor cells is critical for effective socket healing.
• These findings suggest DDR2 as a potential therapeutic target for alveolar bone loss conditions.