# The role of physiologic and pathologic AGEs on RAGE signaling in IVD degeneration

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $336,105

## Abstract

Project Abstract
Degeneration of the intervertebral disc (IVD) is a leading contributor towards back pain, an epidemic that costs
billions of dollars in the US. The IVD consists of a proteoglycan(PG)-rich nucleus pulposus (NP) surrounded
by a collagenous annulus fibrosus (AF) that together provide support and transmit complex loads. The IVD
degenerative cascade involves a multifactorial progression of biological, biochemical, and structural changes
that lead to the collapse of the disc structure and to compromised mechanical function. Despite its significant
public health impact, the pathophysiology of disc degeneration remains unclear.
 The accumulation of Advanced Glycation End-products (AGEs) is associated with aging and
diabetes. Increased AGEs has also been associated with IVD degeneration. AGEs form through
nonenzymatic glycation, where extracellular sugars undergo Maillard rearrangement with amino acids to
become protein adducts and crosslinks. AGES are known to impair the mechanical function of matrix proteins.
Beyond matrix modifications, AGEs activate the cellular Receptor for Advanced Glycation Endproducts
(RAGE), and RAGE signaling perpetuates immune and inflammatory responses. Because the IVD is avascular
and has relatively low tissue remodeling, IVD tissues are susceptible to accumulate AGEs. Despite these
observations, it is not known whether AGEs or RAGE signaling have a causal role in IVD degeneration.
 In this R01 application, we will determine the AGEs- and RAGE-mediated events as disease mechanisms
for IVD degeneration. Specifically, we will identify the role of AGEs in altering IVD structure and function and
define the necessity of RAGE-signaling in AGEs-mediated degeneration. If our hypotheses are supported, this
will provide the putative targets to alleviate the degenerative cascade. The combination of in vivo and ex vivo-
in vitro approaches will enable us to carefully dissect the systemic effects of high AGE-loads from tissue-
specific effects of AGEs. We also will further develop the in vivo contrast-enhanced microCT of the
intervertebral disc as a key technological innovation. This approach provides a resolution that significantly
advances the current state-of-the-art compared to microMRIs. We believe that the successful completion of
the proposed aims will significantly advance our knowledge of intervertebral disc biology and intervertebral disc
imaging.

## Key facts

- **NIH application ID:** 10896118
- **Project number:** 5R01AR074441-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Simon Yue-Cheong Tang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $336,105
- **Award type:** 5
- **Project period:** 2019-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896118

## Citation

> US National Institutes of Health, RePORTER application 10896118, The role of physiologic and pathologic AGEs on RAGE signaling in IVD degeneration (5R01AR074441-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896118. Licensed CC0.

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