# Endogenous retrovirus in joint aging and osteoarthritis development

> **NIH NIH R01** · VAN ANDEL RESEARCH INSTITUTE · 2024 · $610,479

## Abstract

Project Summary/Abstract
Osteoarthritis (OA) is a degenerative disease of the joints, that affects over 16% of people over 60 in the US.
Age and injury are the primary risk factors for OA. There is a critical need to develop therapies for OA
treatment, as current treatment options rely primarily on pain management and joint replacement, while OA is
only becoming increasingly prevalent in our aging population. Chronic exposure to cellular stressors profoundly
disrupts the homeostasis of articular chondrocytes (ACs), the primary cell type covering the surface of the joint,
leading to AC senescence, apoptosis, and degeneration of the smooth surface of the joint. We know that
nuclear changes to chromatin structure impacts the biological age of many tissues and contributes to the
manifestation of aging phenotypes and wanted to investigate whether this is also true in OA. Our preliminary
data suggests that chromatin structure is disrupted in ACs in OA and may be a contributing factor to OA
disease progression.
The overall objective of this proposal is to dissect the mechanism(s) of how aging and stressors influence
chromatin structure to disrupt AC homeostasis to ultimately give rise to OA. Our preliminary findings suggest
that abnormal activation of transposable elements (TEs) occurs preferentially in OA tissue. We hypothesize
that cellular stresses accumulate with age to impair TE silencing in ACs, thereby triggering inflammation and
eventually, OA. We will test our hypothesis: by determining if chromatin accessibility and TE activation
increase with age and presence of osteoarthritis in ACs; by determining if TE activation in OA models can
augment OA progression; and by evaluating if stress causes TE activation and osteoarthritis.
Impact: This project will yield a mechanistic understanding of the connection between aging, stress conditions,
ERV activation, and OA pathogenesis. Importantly, this proposal has the potential to impact joint health and
mobility of our aging population.

## Key facts

- **NIH application ID:** 10899593
- **Project number:** 5R01AG083568-02
- **Recipient organization:** VAN ANDEL RESEARCH INSTITUTE
- **Principal Investigator:** Ting Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $610,479
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899593

## Citation

> US National Institutes of Health, RePORTER application 10899593, Endogenous retrovirus in joint aging and osteoarthritis development (5R01AG083568-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10899593. Licensed CC0.

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