# Role of synovial lining fibroblasts in inflammatory arthritis

> **NIH NIH R21** · EMORY UNIVERSITY · 2023 · $172,150

## Abstract

Project Summary
Fibroblast-like synoviocytes (FLS) are cells, lining of the joint surfaces. They play a critical role in the pathology
of Inflammatory Joint Diseases (IJD), such as rheumatoid arthritis, psoriatic arthritis and juvenile idiopathic
arthritis. Under chronic inflammation, FLS undergo epigenetic remodeling and are transformed into aggressive
cancer-like cells, which evade apoptosis, proliferate, and produce catabolic factors that degrade the articular
cartilage and subchondral bone. Once, transformed, the FLS are known to retain their aggressive properties in
spite of removing them from the inflammatory microenvironment. Epigenetic remodeling is suggested as the
underlying cause. In this proposal, we will focus on a specific subtype of FLS that are located in synovial lining
(L-FLS). Our overarching hypothesis is that the L-FLS function as disease-initiating stem-like cells. We propose
that they act as the initiators and perpetuators of joint degeneration by giving rise to other aggressive FLS
subpopulations and by acquiring long-term epigenetic memory that is implicated in failure to remission. We will
test this hypothesis by determining if the L-FLS possess characteristics, such as, differentiation into another
aggressive subpopulation and retain their epigenetic changes even after resolution of inflammation. In Aim 1 we
will use lineage tracing to identify the L-FLS can give rise to other pathological subtypes. Under Aim 2 we will
investigate if intrinsic epigenetic in L-FLS are irreversible and are responsible for disease persistence. Successful
completion of this proposal will establish L-FLS as IJD-driving cells, which possess the ability to initiate catabolic
changes in the joint as well as confer persistence of the disease phenotype. We anticipate that the L-FLS will be
identified as ideal targets to prevent therapeutic resistance and recurrence of symptoms.

## Key facts

- **NIH application ID:** 10596646
- **Project number:** 5R21AR078463-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Pallavi Bhattaram
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $172,150
- **Award type:** 5
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596646

## Citation

> US National Institutes of Health, RePORTER application 10596646, Role of synovial lining fibroblasts in inflammatory arthritis (5R21AR078463-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10596646. Licensed CC0.

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