# Roles of Type V Collagen in the Structure and Biomechanics of TMJ Condylar Cartilage

> **NIH NIH R21** · DREXEL UNIVERSITY · 2020 · $248,317

## Abstract

PROJECT SUMMARY
 Temporomandibular joint (TMJ) disorder is characterized by the irreversible breakdown of the mandibular
condylar cartilage extracellular matrix (ECM). The condylar cartilage ECM has a specialized bilayer layout of a
fibrocartilage layer covering a secondary hyaline cartilage layer. The development of effective TMJ
regeneration strategies is challenged by our incomplete understanding of how certain molecules in the ECM
are linked to the structure and biomechanical functions of this unique fibrous-hyaline hybrid tissue. This project
will study the roles of collagen V, the regulator of collagen I fibrillogenesis, in the development of condylar
cartilage ECM in vivo. The overall objective is to determine the roles of collagen V in regulating the
establishment of TMJ condylar cartilage ECM during post-natal development. Our central hypothesis is that
collagen V is crucial for proper biomechanical function of the TMJ condylar cartilage, because it regulates the
collagen fibril structure of both the fibrous and hyaline layers.
 To test the central hypothesis, in Aim 1, we will determine the impact of collagen V loss on the formation
and maturation of condylar cartilage. This will be achieved by studying the structural and biomechanical
phenotype of condylar cartilage ECM in global collagen V-knockdown mice, and in our newly established,
cartilage-specific collagen V inducible knockout (cKO) mice under normal TMJ loading. Next, since the
influence of collagen V on the fibrous layer is well known, in Aim 2, we will determine the role of collagen V in
regulating the formation of the hyaline cartilage layer. First, we will test if collagen V impacts the hyaline layer
by altering the load transfer between the fibrous and hyaline layers. This will be achieved by studying if the
phenotype of the hyaline layer in cKO mice is mitigated under reduced TMJ loading in vivo. Second, we will
test if collagen V regulates the chondrogenesis of progenitor cells in the fibrous layer, as well as the resulted
biosynthesis and assembly of hyaline cartilage neo-matrix in the absence of mechanical loading. A number of
innovative approaches will be utilized. Using cKO mice, we will delineate collagen V activities at each stage of
TMJ growth, and minimize confounding effects related to off-target changes of other TMJ tissues. Applying
atomic force microscopy (AFM)-nanomechanical tests, we will quantify the mechanical changes of murine
condylar cartilage as a result of collagen V deficiency. Applying laser capture microdissection with microfluidic
qPCR, we will delineate gene expression profiles of cells in the fibrous versus hyaline layers. Successful
completion of this study will elucidate new molecular activities that govern the formation of the condylar
cartilage ECM, which is necessary for developing tissue engineering and disease intervention strategies to
target this highly specialized, fibrous-hyaline hybrid tissue.

## Key facts

- **NIH application ID:** 10127945
- **Project number:** 1R21DE029567-01A1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Lin Han
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,317
- **Award type:** 1
- **Project period:** 2020-09-16 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127945

## Citation

> US National Institutes of Health, RePORTER application 10127945, Roles of Type V Collagen in the Structure and Biomechanics of TMJ Condylar Cartilage (1R21DE029567-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10127945. Licensed CC0.

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