# Project 2:  Synovial Fluid Proteomics

> **NIH NIH U19** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $921,170

## Abstract

ABSTRACT Project 2: Synovial Fluid Proteomics (previously Project 4)
Osteoarthritis (OA) is the most common form of arthritis and a leading cause of physical disability in older
individuals. There are no approved pharmacologic treatments available beyond those for symptomatic relief and
no biomarkers available to assess disease status or risk of progression. Major reasons for this may include key
differences between blood and intra-articular biomarkers and the dominating influence of biomechanics that
makes it difficult to differentiate systemic from mechanical contributions to OA. There may be differences
between single-site knee and multi-site OA that occurs in hands and knees since the latter may result from
systemic initiation rather than joint-specific factors. Assessment of proteins in joint-specific synovial fluid that is
in direct contact with joint tissues and paired blood plasma may provide insights into joint-specific and systemic
factors in OA. The proposed study will fill a gap in knowledge about the pathobiology of knee and multi-site OA.
The objective of this proposal is to identify novel OA biology underlying knee and multi-site OA using proteomic
analyses of paired synovial fluid and blood plasma. Our central hypothesis is that there are molecular signatures
in synovial fluid and blood plasma that can be used to identify biomarkers for OA and which differentiate systemic
from joint-specific molecular contributors to OA. Our long-term goal is to identify biomarkers that assess OA
burden and disease progression and that provide insights into disease pathogenesis. We will assess returning
participants from the Multicenter Osteoarthritis Study (MOST), a well-characterized prospective cohort of older
individuals aged 54-86 years to assess risk factors for incidence and progression of knee OA. All participants
will undergo radiographic assessments for hand and knee OA at MOST4 Visit 1. Synovial fluid will be collected
in those who have at least 1 ml of synovial fluid present on knee ultrasound (~500 participants), which will include
those with and without frequent knee pain. We will measure proteins in ~500 paired synovial fluid and blood
plasma samples using SOMAScan, an aptamer-based proteomics assay that simultaneously detects ~7,000
proteins. Proteomic findings in MOST will be replicated in an international consortium, STEpUP OA, which
includes ~1,800 individuals from 5 cohorts with proteomic profiling in synovial fluid and plasma. Aim 1 will identify
proteins in knee OA synovial fluid and plasma associated cross-sectionally with knee pain and MRI-detected
cartilage damage. Aim 2 will identify proteins in knee OA synovial fluid and plasma associated with longitudinal
worsening of knee pain or MRI-detected cartilage damage over 24 months. Aim 3 will identify proteins in plasma
associated with multi-site OA. The expected outcome of this proposal is identification of proteomic signatures
that underlie OA pathogenesis. This will be the...

## Key facts

- **NIH application ID:** 10843730
- **Project number:** 5U19AG076471-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** DAVID Tobin FELSON
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $921,170
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843730

## Citation

> US National Institutes of Health, RePORTER application 10843730, Project 2:  Synovial Fluid Proteomics (5U19AG076471-02). Retrieved via AI Analytics 2026-08-17 from https://api.ai-analytics.org/grant/nih/10843730. Licensed CC0.

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