# Pathologic Role of Inflammation and Mechanistic Analysis of Myofibroblastogenesis in Arthrofibrosis

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2021 · $339,306

## Abstract

ABSTRACT
Arthrofibrosis is a very prevalent debilitating complication of routine total knee arthroplasty. Our laboratory
develops mechanism-based strategies for (i) treatment of arthrofibrosis, (ii) early intervention when the disease
process is initiated, and (iii) identification of novel biomarkers that permit the monitoring of disease
progression. We will address a major knowledge gap by addressing the central hypothesis that
arthrofibrosis is initiated in vivo by local alterations in inflammation-related tissue repair processes
after joint surgery. We propose that inflammatory processes modulate formation of mechano-protective
transient connective tissues and that deregulation of normal joint tissue healing results in alterations in the
growth, differentiation and activity of (proto)myofibroblasts that may emerge from the perivascular
compartment of synovial tissues.
To understand the mechanisms contributing to arthrofibrosis, we will analyze (i) the pathologic roles of
inflammatory processes in a rabbit model for arthrofibrosis (Aim 1); and (ii) mechanisms of
myofibroblastogenesis that are deregulated during arthrofibrosis by molecular analyses of biopsies and primary
cell cultures from patients undergoing revision TKAs for arthrofibrosis, as well as established in vitro models for
myofibroblast proliferation and differentiation in culture, as well as co-culture models with mast cells involved in
the initial inflammatory response during tissue repair (Aim 2).
The key deliverables of this proposal are translational innovation (Aim 1) by establishing (i) the mechanistic
role of inflammation in arthrofibrosis and (ii) characterization of the potential efficacy of anti-inflammatory drugs
to mitigate or reverse disease progression. Furthermore, this study is conceptually innovative (Aim 2) by
establishing (iii) cell structure-linked kinase-mediated signaling pathways and gene regulatory networks that
mediate myofibroblast differentiation in joint tissues, and (iv) functional consequences of inhibiting key
regulatory proteins that drive the intrinsic ability of fibroblasts to convert to myofibroblasts.

## Key facts

- **NIH application ID:** 10101481
- **Project number:** 5R01AR072597-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Matthew P Abdel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $339,306
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10101481

## Citation

> US National Institutes of Health, RePORTER application 10101481, Pathologic Role of Inflammation and Mechanistic Analysis of Myofibroblastogenesis in Arthrofibrosis (5R01AR072597-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10101481. Licensed CC0.

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