# Chondrocyte-derived bone cells determine the overall pattern of TMJ condyle and contribute to bone remodeling

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $352,688

## Abstract

TMD (Temporomandibular joint disorders) affect 5-10% of the population in this country, with severe TMD
requiring surgical repair. The cause for TMD is often hard to determine, and the pathophysiology underlying this
affliction remains unclear, as the mandibular condylar cartilage (MCC) differs considerably in its development
and structure from both a growth plate or an articular cartilage. However, the regulation of TMJ development and
growth has been under-studied. Chondrogenesis in the TMJ or limbs has been considered a linked but separate
process from osteogenesis during endochondral bone formation. How can the inherited message be transmitted
from chondrocytes, which supposedly undergo cell death before bone formation, to the cells that form bone?
The answer to this question may lie in recent studies indicating that a direct transformation of chondrocytes to
osteoblasts occurs. Yet, the following key questions remain: how is this cell transformation linked to bone growth
and remodeling? What is the underlying molecular mechanism? Which genes are required for cell
transformation? We propose that chondrogenesis and osteogenesis are one continuous process in which
chondrocyte-derived bone cells (CBC) define the overall pattern of MCC-ramus and contribute to bone
remodeling via Bmpr1a (BMP receptor 1a, a key receptor for BMP2 and BMP4) and -catenin. This hypothesis
is based on: 1) Published data from our lab and others demonstrating that direct cell transformation occurs in
MCC and limbs; 2) Deleting Bmpr1a or -catenin in chondrocytes leads to drastic changes in the condyle and
limbs during growth and bone remodeling, though deletion of either gene in bone cells has little impact on the
skeletal pattern; and 3) The molecular regulation of cell transformation is highly dependent on the skeletal
elements, developmental stage, and different genes. We will test this hypothesis using the following highly
related but independent Aims: 1) To determine molecular regulation of cell transformation by Bmpr1a during
growth and bone remodeling. Working hypothesis: the CBC defines the overall morphology of the condyle and
limbs via BMPR1A that plays variant roles in different elements of the skeleton; and 2): To determine molecular
regulation of cell transformation by -catenin during growth and bone remodeling. Working hypothesis: -catenin
plays variant roles in the condyle vs. limbs in defining skeletal pattern and bone remodeling in a manner that
differs from Bmpr1a; and 3): To determine how chondrocytes demineralize cartilage matrices and form bone
cells ex vivo, and shift expression profiles of genes directly linked to bone cells in vitro. Working hypothesis:
HCs, which migrate, play a dual role in removing calcified cartilage and cell transformation. We expect that CBC
is responsible for most endochondral bone formation and remodeling, regulated by Bmpr1a and -catenin. We
predict that this phenomenon also occurs in limbs, although differentially reg...

## Key facts

- **NIH application ID:** 10058837
- **Project number:** 5R01DE025659-05
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Louis-Bruno Ruest
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $352,688
- **Award type:** 5
- **Project period:** 2016-12-09 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058837

## Citation

> US National Institutes of Health, RePORTER application 10058837, Chondrocyte-derived bone cells determine the overall pattern of TMJ condyle and contribute to bone remodeling (5R01DE025659-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10058837. Licensed CC0.

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