# Mediators of the OA Cascade in the Pre-Arthritic Hip

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2021 · $155,705

## Abstract

PROJECT ABSTRACT
Dr. Cecilia Pascual-Garrido, MD, PhD is a hip preservation and adult reconstruction surgeon whose research
goal is to make significant and meaningful contributions in the care of young adults with pre-OA hip disorders,
through the process of basic scientific discovery and its translation to patient care. Her educational, clinical and
research experiences uniquely prepare her to pursue this work, and this career development award will facilitate
the complementary musculoskeletal research training she requires, with an emphasis on epigenetics,
transcriptome, bioinformatics and statistical concepts. All activities will occur at the Washington University School
of Medicine, an institution with strong health services research program and musculoskeletal research group.
Recent reports indicate an etiologic role of Femoroacetabular Impingement (FAI) in up to 50% of OA cases. Over
300,000 individuals in the US undergo primary total hip replacement (THR) annually, with THR utilization
projected to double by 2030. While characterization of hip bone deformity in FAI has been extensively studied,
the role of intraarticular inflammation and epigenetic changes plays in this disease is unknown. To address this
need, the purpose of this project is to identify critical biologic events that are mediators of the OA cascade in hip
FAI. Aim 1 will identify a catabolic state in articular chondrocytes (ACs) from the impingement zone in hip FAI.
ACs from the impingement zone in FAI (early stage) and OA (late stage) will be tested in cultures with TGF and
IL-1. We hope to characterize a catabolic state and abnormal DNA methylation in pathological cells. Aim 2 will
characterize spectrum of disease (normal-FAI and OA) through gene expression and DNA methylation profile
based. Our preliminary data shows enriched biological processes in hip OA compared to FAI. Additionally, we
will investigate that genome-wide methylation profiling in hip OA and hip FAI. We believe that integrating
epigenomic and transcriptome data will allow us to better understand how the identified loci may contribute to
OA pathogenesis. The application of ATAC-seq in OA is novel and could have tremendous clinical implication to
identify altered promoters and enhancer genes that might be involved in the pathogenesis of hip OA. Finally,
Aim 3 will characterize a small animal model of hip FAI and secondary OA. This animal model could provide a
novel opportunity to test future interventional studies for the treatment of hip OA. Through established
collaboration with musculoskeletal researchers and clinician scientists in our institution, this application has the
potential to uncover early pathological pathways associated with hip OA secondary to hip FAI, which may have
important diagnostic and clinical implications.

## Key facts

- **NIH application ID:** 10254394
- **Project number:** 5K08AR077740-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Cecilia Pascual-Garrido
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $155,705
- **Award type:** 5
- **Project period:** 2020-09-04 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254394

## Citation

> US National Institutes of Health, RePORTER application 10254394, Mediators of the OA Cascade in the Pre-Arthritic Hip (5K08AR077740-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10254394. Licensed CC0.

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