# Modulation of Insertional Achilles Tendinopathy by Multiaxial Mechanical Strains

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $338,800

## Abstract

PROJECT SUMMARY
 Insertional Achilles tendinopathy (IAT) is a debilitating disorder that responds poorly to conservative (non-
surgical) therapies. An effective conservative treatment for this disease must target the fundamental causes of
pathological tissue alterations and induce deformations that promote their reversal. Thus, the objective of this
project is to elucidate the patterns of mechanical strain (i.e., deformation) that cause and reverse IAT in vitro,
and determine how to induce these strain patterns in vivo during exercise-based physical therapy. In
preliminary work, we have used ultrasound elastography to demonstrate that IAT-associated changes are
greater in the deep tendon, where transverse compressive strain |𝜀2𝐺| – compressive strain along the short-axis
of the tendon – is highest due to contact with the heel bone. Moreover, we have determined that tendon
explants loaded under transverse compression in vitro exhibit alterations that resemble IAT. Importantly,
previous studies have demonstrated that transverse compression-induced tendon alterations can be reversed
by axial tensile strain |𝜀1𝐺| (strain along the long axis of the tendon). These findings support our central
hypothesis that deformations with high ratios |𝜀𝐺|/|𝜀𝐺| of transverse compressive strain to axial tensile strain
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cause IAT while deformations with low strain ratios |𝜀𝐺|/|𝜀𝐺| can reverse this disease. To test this hypothesis,
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in Aim 1 we propose to investigate whether high levels of |𝜀𝐺|/|𝜀𝐺| generate IAT-like changes in porcine
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Achilles tendon insertion explants in vitro. In Aim 2, we will investigate whether low levels of |𝜀𝐺|/|𝜀𝐺| can
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reverse IAT-associated changes in human IAT tendon explants in vitro. In Aims 1-2, we will also test the
secondary hypothesis that the differential response of tendon to |εG| and |εG| is due to their markedly different
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effects on tendon cell nuclear volume and shape, a concept supported by preliminary studies. These effects
could lead to distinct alterations in nuclear chromatin organization or nuclear transport that mediate gene
expression and tissue composition. Finally, in Aim 3, we will characterize the mechanical strain patterns
induced by different exercises in vivo and establish how exercises can be adjusted to modulate levels of
|𝜀𝐺|/|𝜀𝐺| in the Achilles tendon insertion. This study will take a significant step towards establishing effective,
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targeted conservative treatment for patients with IAT. Moreover, the findings and approaches established in
this proposal could also be applicable to other important tendon and ligament diseases including rotator cuff
disease, carpal tunnel syndrome and patellar tendinopathy.

## Key facts

- **NIH application ID:** 9934990
- **Project number:** 5R01AR070765-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Mark Raymond Buckley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $338,800
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934990

## Citation

> US National Institutes of Health, RePORTER application 9934990, Modulation of Insertional Achilles Tendinopathy by Multiaxial Mechanical Strains (5R01AR070765-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934990. Licensed CC0.

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