The Zonal Architecture of the Mandibular Condyle Requires ADAMTS5

Area of Science:

• Biochemistry
• Developmental Biology
• Orthopedics

Background:

• Temporomandibular joint osteoarthritis (TMJOA) involves extracellular matrix (ECM) disruption and cartilage degradation.
• Upregulated a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 cleaves aggrecan (Acan) and is a TMJOA hallmark.
• Research on ADAMTS5-Acan turnover has primarily focused on hyaline cartilage, not the TMJ's fibrocartilage.

Purpose of the Study:

• To investigate the role of ADAMTS5 in the development of the mandibular condylar cartilage (MCC) zonal architecture.
• To test the hypothesis that ADAMTS5 is essential for proper MCC development.

Main Methods:

• Harvesting Adamts5^+/+ and Adamts5^-/- murine TMJs at various postnatal ages (P7, P21, 2 mo, 6 mo).
• Histomorphometrics to assess ECM volume.
• Immunohistochemistry and Western blots for Acan localization.
• Quantitative real-time PCR for chondrogenic maturation markers (Col2a1, Col10a1, Sox9).
• Modified Mankin scoring for TMJOA assessment.

Main Results:

• Adamts5^-/- mice exhibited increased ECM and Acan accumulation in the MCC.
• Reduced cell volume and less mature hypertrophic chondrocytes were observed in Adamts5^-/- MCC.
• Significant reduction in chondrogenic maturation markers (Col2a1, Col10a1, Sox9) in Adamts5^-/- MCC.
• Older Adamts5^-/- MCC showed altered chondrogenic cell arrangements and early TMJOA characteristics.

Conclusions:

• ADAMTS5 plays a critical role in hypertrophic chondrocyte maturation and establishing MCC zonal architecture.
• Disruption of ADAMTS5 function leads to ECM dysregulation and may cause early-onset TMJOA.
• This study highlights a novel function of ADAMTS5 in TMJ development and fibrocartilage homeostasis.