# Targeting P21 positive senescent cells for alleviating TMJ degeneration

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2024 · $399,198

## Abstract

Abstract
Temporomandibular Joint (TMJ) degeneration is a painful and debilitating disease of the synovial joint,
affecting over 20 million people in the United States. Obesity, advancing age and mechanical loading are
greatest risk factor for many diseases including TMJ degeneration. TMJ degeneration significantly impair the
quality of life by causing acute and chronic pain, thus making this disease a global health issue and a financial
burden of epidemic proportion. The incidence of the TMJ degeneration is expected to rise substantially as the
prevalence of obesity has risen dramatically over the last two-decades. As there is no effective treatment for
the TMJ degeneration in an obese and aged individual, there is an unmet clinical need for an effective
approach to treat TMJ degeneration.
The current proposal seeks to address this unmet clinical challenge using a highly innovative approach of
targeting p21 high cells both genetically and therapeutically for the treatment of TMJ degeneration. Our
overarching hypothesis is that p21 high cells plays a central role in obesity, age-related and mechanical loading
induced TMJ degeneration and targeted elimination of the p21 high cells may alleviate TMJ degeneration. To
test this hypothesis, we will define: (1) the role of p21 high cells in osteochondral tissue in obesity and aging
induced TMJ degeneration. Using a novel inducible p21-cre ERT2 X td-Tomato mice we will examine the
effects of p21 high cells on the homeostasis of the osteochondral tissues of the TMJ in obesity and aging. (2)
the pathophysiological mechanism by which p21high cells causes TMJ degeneration. Using the novel mice
model (p21-cre ERT2 X td-Tomato X Rela flox/flox), we will examine the effect NF-κB pathway on the senescent
cells in TMJ degeneration. 3) To define the role of p21high cells in traumatic TMJ injury and repair. p21-cre
ERT2 X td-Tomato mice will be subjected to traumatic injury to TMJ and we will genetically clear the p21 high
cells after traumatic injury to see whether we can alleviate TMJ-OA or repair the damaged cartilage. A
combination of mechanical, immunohistochemical, molecular biology and histomorphometric techniques
coupled with novel genetic mice models will be used to study the proposed specific aims.
The proposed project has the immense potential to reveal new regulatory pathways that controls homeostasis
of the osteochondral tissues of the TMJ in an obese and aged individual and to open new insight on
understanding the disease mechanism and developing therapeutic interventions.

## Key facts

- **NIH application ID:** 10890439
- **Project number:** 1R01DE033004-01A1
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Sumit Yadav
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $399,198
- **Award type:** 1
- **Project period:** 2024-09-05 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890439

## Citation

> US National Institutes of Health, RePORTER application 10890439, Targeting P21 positive senescent cells for alleviating TMJ degeneration (1R01DE033004-01A1). Retrieved via AI Analytics 2026-07-28 from https://api.ai-analytics.org/grant/nih/10890439. Licensed CC0.

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