# Extracellular Matrix Regulation of Inflammatory Signaling in Tendon

> **NIH AR R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2026 · $326,040

## Abstract

Abstract
 Twenty percent of all primary care consults are related to musculoskeletal diseases; 30% of these are
associated with tendinopathies. Pathogenesis of tendinopathy includes increased inflammatory signaling and
extracellular matrix (ECM) remodeling. This remodeling leads to softer tendinopathic tendons, increasing the
risk of tearing. Yet the relative roles of chronic inflammation and ECM stiffness in the initiation and progression
of tendon disease remain controversial and are difficult to decouple in patient populations. We and others have
shown that, in 2D cell culture using interleukin-1β (IL-1β) as a stimulant, patient-derived tendinopathic
fibroblasts exhibit a stronger inflammatory response that is further enhanced on soft substrates. This
inflammatory response is dependent on NF-κB signaling, which we have previously established as a critical
regulator of tendon disease and healing. Yet these studies are limited by the use of classical 2D culture
approaches and fail to recapitulate in vivo cell behavior or provide insight into ECM remodeling. The ability to
visualize cytokine receptor clustering in 3D environments has further demonstrated that cellular sensitivity to
cytokines is based on the properties of the ECM. Although these studies suggest physicochemical coupling
between ECM stiffness (physical) and inflammatory signaling (chemical) that sustains chronic loss of tendon
mechanical function, the mechanisms of how ECM drives cell behavior in 3D tissues like tendon remain
unknown. Therefore, there remains a critical need to define the physicochemical cell-ECM interactions that
regulate tendon function to discover the mechanisms underlying tendinopathies and treatments. Our long-term
goal is to develop therapeutic strategies for the clinical treatment of tendinopathy by identifying key cell-ECM
mechanisms driving chronic inflammatory tendon disease. Our overall objective in this application is to develop
a novel approach to studying the physicochem

## Key facts

- **NIH application ID:** 11262219
- **Project number:** 5R01AR083343-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Adam Christopher Abraham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AR
- **Fiscal year:** 2026
- **Award amount:** $326,040
- **Award type:** 5
- **Project period:** 2024-04-05T00:00:00 → 2029-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11262219

## Citation

> US National Institutes of Health, RePORTER application 11262219, Extracellular Matrix Regulation of Inflammatory Signaling in Tendon (5R01AR083343-03). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11262219. Licensed CC0.

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