# The mechanistic role of increased glycosaminoglycans in post-fatigue damaged tendons

> **NIH NIH R21** · CORNELL UNIVERSITY · 2020 · $174,175

## Abstract

Tendinopathies are common musculoskeletal injuries that often lead to tendon rupture and loss of function. An
increase in glycosaminoglycan (GAGs) content is one of the most prominent characteristics of late stage
tendinopathy. Despite the prevalence of this observation in clinical patients, a fundamental question still remains:
is the increase in GAGs that is characteristic of late stage tendinopathy a result of the altered cellular loading
environment or part of the mechanistic pathway by which cells modulate the altered loading environment to
maintain survival and homeostasis? Answering this question is critical, as it would inform whether the goal for
effective interventions should aim to increase or decrease GAG content post sub-rupture fatigue damage injury
in order to halt or reverse the progression of damage. Interestingly, using our established in vivo model of sub-
rupture damage accumulation in the patellar tendon (PT) to investigate the onset and pathogenesis of
tendinopathy, we have found that the increase in GAGs, particularly dermatan sulfate (DS) and hyaluronan (HA),
that is associated with late stage tendinopathy initiates after just 1 bout of fatigue loading. We have also found
that physiological exercise that is initiated prior to the increase in DS and HA leads to further degeneration, but
exercise that is initiated after the increase in DS and HA promotes remodeling. These findings highlight the
potential contribution of GAGs to the capacity of the tendon to repair and suggests that investigating their role in
our model will ultimately motivate diagnostics to guide clinical management of fatigue damaged tendons.
Accordingly, this proposal will test the hypothesis that the early increase in DS and HA modulates the mechanical
environment of the resident cells to restore interactions with the extracellular matrix (ECM) and promote survival;
a mechanistic necessity for the fatigue damaged tendon to repair from subsequent therapeutic loading. We will
determine the effect of the increase in DS and HA post fatigue loading on (1) multi-scale tendon mechanics and
the mechanical environment of the cells (Aim 1); and (2) promotion of cell survival, maintenance of cell
phenotype, and modulation of the biological environment that may be necessary for an effective response to
therapeutics after fatigue injury (Aim 2). We will utilize our fatigue damage model in combination with novel
imaging applications and visualization of deformations of GFP+ cells with post mortem (Aim 1) and in vivo (Aim
2) digestion of HA and DS. The proposed studies will propel progress in the field by providing goals for
therapeutics regarding modulation of GAGs in fatigue damaged tendons. In addition, these studies will be
foundational to establishment of diagnostic tools to guide clinicians as to whether a patient will benefit from
exercising a fatigue damaged tendon or will incur further injury; a major step towards advancement of patient
specific management of ...

## Key facts

- **NIH application ID:** 9964678
- **Project number:** 5R21AR074602-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** NELLY Andarawis-Puri
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $174,175
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964678

## Citation

> US National Institutes of Health, RePORTER application 9964678, The mechanistic role of increased glycosaminoglycans in post-fatigue damaged tendons (5R21AR074602-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9964678. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*