# Cell-Matrix Regulation of Fibrochondrocytes  In TMJ OA

> **NIH NIH R56** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $432,880

## Abstract

ABSTRACT
Cell-matrix regulation of fibrochondrocytes in TMJ OA
Disorders of the temporomandibular joint (TMJ) affect between 3-7% of the population and osteoarthritis (OA)
is the most common pathology associated with TMJ dysfunction. TMJ OA is a disease of cartilage
degeneration and chondrocyte apoptosis. One of the key factors leading to chondrocyte apoptosis is the
suppression of the cytoprotective process of autophagy. Autophagy is one of the earliest cellular responses to
TMJ OA and has been shown to be a viable therapeutic target for attenuating the progression of cartilage
degeneration. A major gap in knowledge is how mechanical and inflammatory stress leads to the eventual
suppression of autophagy, apoptosis, and cartilage degeneration. To address this gap, my lab has developed
expertise in a preclinical, surgical induction mouse model of TMJ OA that closely corresponds to the human
condition and identified a three-step pathogenesis model linking mechanical damage to ECM changes and
chondrocyte apoptosis that includes 1) the depletion of Collagen VI (Col VI) following surgically-induced TMJ
OA 2) the proteolysis of a Col VI chondrocyte receptor, Neuron/Glial antigen 2 (NG2) and 3) the reduction of
autophagy. The overall goal of our study is to test the hypothesis that injury-induced Col VI degeneration
activates an NG2-dependent pathway that accelerates TMJ cartilage degeneration by suppressing autophagy.
Based on the preliminary data included in this application, we have designed a research plan to
mechanistically define how NG2 binding with Col VI is necessary for the maintenance of autophagy and how
NG2 monoclonal antibody therapy can attenuate the progression TMJ cartilage degradation by protecting
autophagy. The proposed work is innovative because it focuses on a novel molecular mechanism of
chondrocyte function that contextually links matrix dysfunction with loss of a cytoprotective cellular mechanism
implicated in the progression of TMJ OA. The significance of this research lies in the potential application to the
clinical problems of TMJ OA and represents a leap forward in our knowledge of TMJ OA pathophysiology. We
anticipate that the outcomes of our study will inform new therapeutic approaches that attenuate the
progression of TMJ OA and restore TMJ health in patients that would otherwise require alloplastic total joint
replacement.

## Key facts

- **NIH application ID:** 10214992
- **Project number:** 1R56DE029835-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** David Andrew Reed
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,880
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214992

## Citation

> US National Institutes of Health, RePORTER application 10214992, Cell-Matrix Regulation of Fibrochondrocytes  In TMJ OA (1R56DE029835-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10214992. Licensed CC0.

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