# Targeting Cellular Mechanosensing to Alleviate Joint Stiffness in Synovial Fibrosis

> **NIH VA I21** · PHILADELPHIA VA MEDICAL CENTER · 2022 · —

## Abstract

Joint pain and stiffness associated with osteoarthritis and synovial fibrosis affects a large population of active
duty military and veterans with an incidence higher than the general public. Despite the prevalence of disease,
there are currently no non-surgical treatments with significant disease-modifying capabilities, and consequently
end stage disease culminates in total knee arthroplasty. The research goal of this proposal is to develop and
test a non-surgical intervention to alleviate joint stiffness and protect the joint’s cartilage surfaces. In synovial
fibrosis, fibroblast to myofibroblast differentiation leads to joint stiffening via cell-mediated extracellular matrix
deposition and reorganization. Additionally, this fibrotic differentiation of synovial fibroblasts leads to reduced
lubricant secretion into the synovial fluid. Mechanosensing, or a cell’s interpretation of the mechanical
microenvironment, is a crucial facet of fibrosis development and may potentially pose a therapeutic target. In this
proposal, we will target synovial cell contractility, or how much a cell pulls on its local environment, to introduce
a therapy that can both mitigate fibrotic cell differentiation and restore lubricant expression in joints. We will test
our hypothesis that modulating cellular mechanosensing can inhibit synovial fibrosis using two Aims. In the first
Aim, we will assess how a microsphere-delivered small molecule, fasudil, can inhibit fibrotic behaviors of synovial
fibroblasts collected from total knee arthroplasty patients. In the second Aim, we will assess this treatment using
a rabbit model of synovial fibrosis induced via joint injury and immobilization. This Aim will test two treatment
strategies by introducing the treatment in the incubation periods of disease following injury and also after the
onset of fibrosis at the time of remobilization. Overall, this work has the potential to introduce a new treatment
option for veterans experiencing joint pain and stiffness that can delay the need for surgical intervention.

## Key facts

- **NIH application ID:** 10475464
- **Project number:** 1I21RX003854-01A1
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Carla Rose Scanzello
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475464

## Citation

> US National Institutes of Health, RePORTER application 10475464, Targeting Cellular Mechanosensing to Alleviate Joint Stiffness in Synovial Fibrosis (1I21RX003854-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10475464. Licensed CC0.

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