# Mechanobiology of Inflammation in the Intervertebral Disc

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $326,730

## Abstract

Project Summary:
Disability and pain stemming from degenerated intervertebral discs (IVD) affects over 40% of U.S
adults and costs >$100 billion annually. The etiology of IVD degeneration (DD) is unknown. There is
a significant clinical need for a better mechanistic understanding of DD, and for therapeutic
approaches that directly treat the IVD, mitigate DD, and promote recovery of spine function.
I
nflammation is a key contributor to discogenic pain. High mobility group box 1 (
HMGB1) protein is a
ubiquitous nuclear protein that is secreted extracellularly by stressed or dying cells. The biologic
function of HMGB1 depends on its cellular location, redox state, and binding partners. Recent studies
show that HMGB1 levels increase with DD severity, though the biologic function of HMGB1 in nucleus
pulposus (NP) cells and its role in DD are largely unknown. The contributions of HMGB1 to NP cell
mechanobiology are similarly unknown, and may be dually related to the pro-inflammatory potential of
disulfide HMGB1 and to the chemotactic activity of fully reduced HMGB1. The objective of the
proposed studies is to identify the redox dependent function of HMGB1 in DD. Our global hypothesis
is that HMGB1 will trigger IVD pro-inflammatory signaling, promote ECM degradation and alter NP
cell mechanobiology in a redox dependent manner. Aim 1 studies will quantify the biological and
mechanotransduction function of redox isoforms of HMGB1 in human NP cells. We will also identify
the specific binding receptors that mediate the pro-inflammatory and mechanobiological activity of
HMGB1 isoforms in NP cells. Aim 2 studies will identify the contribution of HMGB1 as a central
mediating damage associated molecular pattern (DAMP) in DD inflammation and mechanobiology
from acute to chronic stages in vivo. These studies will provide mechanistic evidence about how
redox isoforms of HMGB1 contribute to DD and mechanotransduction. Our findings may identify
targets for mitigating DD initiation or progression. Since multiple HMGB1 isoforms have the potential
to alter the cytoskeleton and thus mechanobiology of NP cells, we predict that our studies will identify
strategies for mitigating alterations in IVD mechanotransduction, which are more extensive than
regulating inflammatory signaling.

## Key facts

- **NIH application ID:** 10236334
- **Project number:** 5R01AR069668-06
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** NADEEN O. CHAHINE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,730
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10236334

## Citation

> US National Institutes of Health, RePORTER application 10236334, Mechanobiology of Inflammation in the Intervertebral Disc (5R01AR069668-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10236334. Licensed CC0.

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