FSP1/S100A4-Expressing Stem/Progenitor Cells Are Essential for Temporomandibular Joint Growth and Homeostasis

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Orthopedics
• Cartilage Biology

Background:

• Temporomandibular joint (TMJ) disorders often stem from cartilage defects.
• The condyle's superficial layers are hypothesized to harbor stem/progenitor cells for mandibular growth and homeostasis.
• Identifying these stem cells is critical for understanding TMJ development and disease.

Purpose of the Study:

• To investigate the role of fibroblast-specific protein 1 (FSP1) as a marker for TMJ condylar stem/progenitor cells.
• To determine the contribution of FSP1-expressing cells to condylar growth and maintenance.
• To elucidate the relationship between FSP1-expressing cells, Wnt signaling, and TMJ osteoarthritis.

Main Methods:

• Lineage tracing using FSP1-Cre;R26RmTmG mice to track FSP1-expressing cell fate.
• BrdU pulse-chase experiments to identify label-retaining stem/progenitor cells.
• Conditional diphtheria toxin-induced ablation of FSP1-expressing cells in FSP1-Cre;R26RDTA mice.
• Analysis of Wnt/β-catenin activity in FSP1-expressing cells.

Main Results:

• FSP1-expressing cells are restricted to the superficial zone and give rise to all condylar layers, confirming their stem/progenitor identity.
• FSP1 labels a novel population of label-retaining stem/progenitor cells within the TMJ condyle.
• Destruction of FSP1-expressing cells leads to severe TMJ osteoarthritis and cartilage loss.
• FSP1 expression is associated with reduced Wnt activity; Wnt activation downregulates FSP1 and causes cartilage loss.

Conclusions:

• FSP1-expressing cells in the superficial zone are essential for TMJ condylar growth and maintenance.
• These FSP1+ stem/progenitor cells play a critical role in preventing TMJ osteoarthritis.
• Regulation of Wnt activity within FSP1-expressing cells is crucial for preserving TMJ condylar cartilage integrity.