# Achilles Tendinopathy Center of Research Translation

> **NIH NIH P50** · UNIVERSITY OF PENNSYLVANIA · 2024 · $31,926

## Abstract

ABSTRACT
Current treatment strategies for Achilles tendinopathy seek to modulate the tendon mechanical environment to
promote healing and regeneration. However, a lack of fundamental understanding of tendinopathic
mechanobiology limits optimization of rehabilitation strategies and impedes development of targeted mechano-
therapeutics. This proposal will address these gaps using orthogonal experiments across human tendinopathy,
rat overuse, and mechanistic mouse models. The proposed studies will establish a framework to inform
mechanotherapeutic strategies and identify novel signaling targets. Tendinopathy, particularly caused by
overuse, often results in tissue microdamage. This microdamage, in turn, impairs transmission of tensile
mechanical signals through the tissue, resulting in under-loading of endogenous tendon cells. Our preliminary
data show that tendon cells exhibit a biphasic response to tendon de-tensioning. De-tensioning causes a
transient loss in cytoskeletal tension and mechanotransductive signaling, resulting in upregulation of matrix
degrading enzymes like matrix metalloproteinases. Subsequently the tendon cells attempt to re-tension the
matrix by cytoskeletal contraction and matrix re-organization. This biphasic response represents a novel
framework for understanding the development, progression, and translational intervention of tendinopathy. In
the proposed studies, we will 1) determine how tendinopathic disease impacts Achilles tensional homeostasis
across the spectrum of disease, 2) define the mechanotransductive mechanisms, and 3) determine how
rehabilitative loading restores Achilles tensional homeostasis for translational impact. Using our expertise in
tenogenesis and tendinopathy (Dyment) and mechanobiology (Dyment/Boerckel), this translational project will
provide a comprehensive understanding of the mechanotransductive mechanisms that drive aberrant and
chronic matrix remodeling during Achilles tendinopathy, define mechano-response benchmarks in controlled
assays that may predict clinical patient outcome, and identify potent drug targets for the next generation of
tailored mechanotherapeutics to complement the current gold standards of physical therapy and surgery.

## Key facts

- **NIH application ID:** 11075460
- **Project number:** 3P50AR080581-02S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** LOUIS J SOSLOWSKY
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $31,926
- **Award type:** 3
- **Project period:** 2024-09-20 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11075460

## Citation

> US National Institutes of Health, RePORTER application 11075460, Achilles Tendinopathy Center of Research Translation (3P50AR080581-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11075460. Licensed CC0.

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