PRRX1⁺MSCs Enhance Mandibular Regeneration during Distraction Osteogenesis

Area of Science:

• Regenerative Medicine
• Orthopedic Surgery
• Stem Cell Biology

Background:

• Bone defects (BD) cause significant physical limitations.
• Distraction osteogenesis (DO) is effective for bone regeneration, but its mechanism is unclear.
• Understanding cellular mechanisms in DO is crucial for improving bone defect treatments.

Purpose of the Study:

• To elucidate the cellular mechanisms underlying bone regeneration in distraction osteogenesis.
• To compare cellular differences between distraction osteogenesis and bone defect calluses.
• To identify key cell populations and molecular pathways involved in DO-mediated bone regeneration.

Main Methods:

• Established canine models for distraction osteogenesis (DO) and bone defects (BD).
• Utilized micro-computed tomography, histological staining, and single-cell RNA sequencing.
• Isolated and characterized mesenchymal stem cells (MSCs); employed CRISPR/Cas9 for gene knockout.

Main Results:

• DO significantly increased mineralized bone volume and new bone formation compared to BD.
• Mesenchymal stem cells (MSCs) from DO calluses exhibited stronger osteogenic capability than those from BD.
• Identified 6 major cell populations, including PRRX1+ MSCs, with specific subpopulations expressing neural crest cell markers in DO.

Conclusions:

• PRRX1+ MSCs, particularly those maintaining an embryonic-like state via continuous distraction, are essential for jawbone regeneration.
• Loss of PRRX1 function in MSCs blunts osteogenesis, migration, and proliferation, impairing bone regeneration.
• This study provides a cellular atlas of DO regeneration, highlighting the critical role of PRRX1+ MSCs.