# Role of the cartilage endplate in spinal disc degeneration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $348,700

## Abstract

PROJECT SUMMARY
Low back pain is the leading cause of disability, and is closely linked to disc degeneration. Poor disc nutrition is
a key factor involved in degeneration onset and progression, and is a major obstacle that could hinder the
success of biologic therapies. The premise of this new project is that low cartilage endplate (CEP) permeability
limits disc nutrient supply and cell function, and that we can identify patients with adequate nutrient supply who
might benefit from biologic therapy through non-invasive assessment of CEP permeability. We propose
innovative studies in cells, tissues, and human subjects that will: 1) identify critical values of CEP permeability
needed for nutrient and metabolite transport under static and dynamic loads; 2) discover compositional and
microstructural characteristics that hinder solute transport; 3) validate MRI techniques that are sensitive to
these characteristics; and 4) determine the clinical relevance of low CEP permeability in human subjects.
Three complementary aims are proposed. In Aim 1 we will develop a quantitative relationship between CEP
permeability, cell density, and disc cell function using a novel in vitro diffusion chamber. By incubating the
chambers with cadaveric CEP samples with a wide range of permeabilities, we will establish critical values of
CEP permeability necessary to sustain cell densities associated with healthy discs. We will also quantify how
dynamic loads enhance solute transport across the CEP and discover the range of CEP permeabilities and
solute sizes where transport enhancement is greatest. In Aim 2 we will determine the relationship between
solute transport and various measures of CEP biochemical composition, matrix porosity, and organization. This
knowledge will provide a mechanistic link between CEP composition and disc health. In Aim 3 we will test the
clinical relevance of low CEP permeability in human subjects using a combination of new MRI techniques that
are sensitive to CEP permeability and disc cell metabolic stress. We will also compare the relative
contributions of low CEP permeability vs. poor vascularity. The results from these studies will address an
unmet clinical need and exert a broad impact by: 1) providing validated tools and a mechanistic framework to
determine the role of CEP permeability in disc degeneration severity; 2) establishing the first non-invasive
selection criteria to identify discs that can support the higher nutrient demands required by biologic therapies;
and 3) guiding development of new treatments that improve disc health by enhancing CEP permeability.

## Key facts

- **NIH application ID:** 9850530
- **Project number:** 5R01AR070198-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Aaron J Fields
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,700
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850530

## Citation

> US National Institutes of Health, RePORTER application 9850530, Role of the cartilage endplate in spinal disc degeneration (5R01AR070198-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850530. Licensed CC0.

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