# Role of serum advanced glycation end-products in altering tendon properties with diabetes

> **NIH NIH R01** · PURDUE UNIVERSITY · 2024 · $588,861

## Abstract

PROJECT SUMMARY
Impaired tendon biomechanical function reduces mobility and quality of life for the majority of the ~30 million
Americans with diabetes, resulting in a substantial economic burden to these individuals and society. Any new
approach to enhancing tendon function in people with diabetes is hindered by a poor understanding of the
underlying etiology of impaired tendon biomechanical properties. Critically, the role that various serum factors
play in the development of tendon complications in individuals with diabetes remains unclear. Our
multidisciplinary research team hypothesizes that increased serum advanced glycation end-products (AGEs),
with subsequent activation of receptors for AGEs (RAGE), is a principal mechanism driving tendon
complications with diabetes. Specifically, activation of RAGE impairs tenocyte function resulting in loss of
collagen fibril organization and subsequent impairment of biomechanical function. AGEs accumulate in the
serum of patients with diabetes. Our preliminary cell culture work shows that treating tendon-derived cells with
AGEs, which cannot form collagen crosslinks, adversely affects critical aspects of tendon ECM maintenance.
We have also found that AGEs promote an environment favoring tendon ECM degradation. Utilizing human
subjects, we demonstrate that increasing serum AGE concentrations are associated with declining tendon
biomechanical properties (e.g., modulus). Serum AGEs can interact with RAGE to promote inflammation and
oxidative stress, but such a connection to changes in tendon ECM organization and biomechanical function
impairment has not been established. This project aims to 1) delineate the role of serum AGEs and activation
of RAGE in promoting tendon ECM disorganization and impairment of biomechanical properties and 2)
determine the relationship of serum AGEs to in vivo tendon biomechanical properties and in vivo indicators of
tendon collagen fibril organization. Filling these gaps will promote new approaches for improving tendon
function and reducing this challenging clinical condition's economic and social burden. Using a mouse model
with an inducible RAGE deletion and a model of type 2 diabetes, we will assess the effects of chronically
elevated serum AGEs on tendon ECM organization and biomechanical function and the involvement of RAGE
in this process. We will use novel ultrasound and magnetic resonance imaging (MRI) methods to determine the
relationships between serum AGE concentrations, in vivo tendon modulus, and MRI indicators of tendon ECM
organization. We expect this work to show that AGEs via RAGE signaling are a principal mechanism driving
changes in tendon ECM and subsequent reduction in biomechanical function in patients with diabetes.
Defining the role of serum AGEs and RAGE signaling in the development of the diabetic tendon phenotype will
provide an avenue to evaluate novel treatment approaches to reduce the impact of tendon complications in
patients with diabetes. Our...

## Key facts

- **NIH application ID:** 10934566
- **Project number:** 5R01AR081967-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Chad Clayton Carroll
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $588,861
- **Award type:** 5
- **Project period:** 2023-09-25 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10934566

## Citation

> US National Institutes of Health, RePORTER application 10934566, Role of serum advanced glycation end-products in altering tendon properties with diabetes (5R01AR081967-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10934566. Licensed CC0.

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