# Identifying the cellular origins of jaw joint cartilage regeneration in zebrafish

> **NIH NIH F31** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $43,737

## Abstract

PROJECT SUMMARY
Temporomandibular jaw joint osteoarthritis (TMJ OA) and other disorders of the TMJ affect up to 12% of the US
population. OA in general is the leading cause of disability in the US and is characterized by the deterioration of
the superficial cartilage lining the joints. A contributor to the high incidence of TMJ OA is the fact that humans
are unable to regenerate the specialized superficial cartilage of joints. Current treatments are limited to
minimizing pain instead of restoring natural joint structure and function. The Crump lab has recently shown that
adult zebrafish can regenerate the superficial cartilage of the synovial jaw joint after injury. This model relies on
transecting a major ligament supporting the jaw, which results in joint degeneration in the short term and full
regeneration of the superficial cartilage lining the jaw joint after the ligament heals. The limitations of this surgical
model are that it is labor-intensive, low-throughput, and highly variable. Using an f13a1b enhancer which we
discovered drives highly specific activity in superficial cartilage of the jaw and other neural crest-derived joints, I
have generated transgenic lines to specifically ablate joint cartilage. Using this ablation model, I have found that
jaw joint superficial cartilage regeneration is highly reproducible, and this will allow me to investigate the source
of new cartilage cells. For this proposal, I plan to optimize the transgenic model for joint cartilage ablation, and
then investigate the sources of the regenerating cartilage. To do so, I have identified through single-nuclei
chromatin accessibility studies several cell type-specific enhancers that will allow me to mark and lineage trace
putative progenitors during joint regeneration. Three potential sources of regenerated joint chondrocytes will be
investigated: 1) The perichondrium surrounding the jaw joint could house progenitor cells that move into the joint
upon ablation and form new superficial chondrocytes. 2) Deeper chondrocytes at the joint, which share properties
with growth plate chondrocytes, could transdifferentiate into superficial chondrocytes following ablation. 3) Rare
superficial chondrocytes that escape ablation could proliferate and repopulate the joint surface. Using newly
identified cell type-specific enhancers, I will create CreERT transgenic lines to trace the contributions of each
population during jaw joint cartilage regeneration. In parallel, I will carry out a single-cell multiomic analysis of
the regenerating jaw joint to discover in an unbiased way potential progenitor cells activated by injury that may
mediate repair. By identifying the source of jaw joint cartilage regeneration in zebrafish, I will be poised to further
explore the molecular basis by which zebrafish can regenerate their joint tissues. In the future, we hope to
uncover whether similar populations exist in the human TMJ that can be activated to counteract OA.

## Key facts

- **NIH application ID:** 10999215
- **Project number:** 1F31DE034307-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Oluchi Amarachukwu Ebere Ofoegbu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,737
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-06-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999215

## Citation

> US National Institutes of Health, RePORTER application 10999215, Identifying the cellular origins of jaw joint cartilage regeneration in zebrafish (1F31DE034307-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10999215. Licensed CC0.

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