# The Role of Inflammation in Knee Osteoarthritis

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $158,760

## Abstract

Project Summary:
Symptomatic knee osteoarthritis (OA) affects 14 million adults in the U.S. and is a leading cause
of disability. There is growing recognition of distinct phenotypes within OA and the need to tailor
therapies to specific phenotypes. Intra-articular inflammation manifesting as synovitis has
emerged as an important phenotypic feature associated with pain and structural progression.
This proposal centers on understanding the role of synovitis and its topographic and temporal
effects on pain as well as its potential as a treatment target. The first aim investigates whether
discordance in effusion-synovitis between an individual’s knees portends differential pain
reporting between the knees. Longitudinally we will investigate whether changes in synovitis
over 24 months are associated with changes in pain. These analyses will include adjustment for
both knee and individual level contributors to pain to better ascertain the independent effect of
synovitis on pain. The second aim uses ultrasound, a readily available and inexpensive imaging
technique, to examine whether the presence of effusion-synovitis in the knee identifies a
subgroup that will have a greater reduction in pain after intra-articular steroid injection. Lastly,
aim 3 will utilize single-cell RNA sequencing of the synovium in patients with mild, moderate and
severe OA to better define cell types and transcriptional profiles active at various OA stages. If,
as we suspect, inflammation is more predominant early in the disease process, anti-
inflammatory therapies may be most effective in early OA.
This funding opportunity and project are specifically geared toward my transitioning to an
independent investigator and R01 funding. I will have protected time for this project and a
uniquely supportive and rich academic environment with access to world-leading mentors,
coursework, and career development series through the Harvard Medical School, Harvard T.H.
Chan School of Public Health and Brigham and Women’s Hospital. Specifically, the aims in this
proposal will provide experience with advanced hierarchical, clustered and longitudinal
statistical modeling, use of ultrasound and magnetic resonance imaging variables in analysis,
and RNA sequencing of the synovium. These aims and educational opportunities will give me
an in-depth understanding of methods to investigate key facets of inflammation in OA,
positioning me to lead future work on the timing and targeting of novel OA therapies.

## Key facts

- **NIH application ID:** 10795946
- **Project number:** 5K23AR080206-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Lindsey A. MacFarlane
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $158,760
- **Award type:** 5
- **Project period:** 2022-04-01 → 2024-12-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795946

## Citation

> US National Institutes of Health, RePORTER application 10795946, The Role of Inflammation in Knee Osteoarthritis (5K23AR080206-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10795946. Licensed CC0.

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