# Potential Role of Mast Cells in Intervertebral Disc Ageing, Herniation Resolution, and Degeneration: Evidence and Lessons Learned from Studies of Mast Cells in Other Connective Tissues

**Authors:** David A. Hart

PMC · DOI: 10.3390/ijms27062804 · International Journal of Molecular Sciences · 2026-03-19

## TL;DR

This paper explores how mast cells might contribute to intervertebral disc aging and degeneration, suggesting mast cell stabilizers could be a treatment option.

## Contribution

The paper proposes mast cell stabilizers like ketotifen as potential treatments for intervertebral disc degeneration.

## Key findings

- Mast cells are present in the intervertebral disc and increase in degenerative conditions.
- Mast cell stabilizers may help preserve disc integrity in chronic degenerative diseases.
- Combining mast cell targeting with proteinase inhibitors could enhance treatment effectiveness.

## Abstract

In the body, mast cells are found in the circulation and located in tissues. These immune cells arise in the bone marrow and are often associated with conditions such as allergies and asthma. However, these cells also play roles in other inflammatory reactions, dysregulated wound healing and chronic conditions. Regarding their presence in tissues of the intervertebral disc (IVD), mast cells have been located in the normal nucleus pulposus, and reports indicate mast cell numbers are elevated in IVD degenerative conditions. As the integrity of the IVD is reported to decline with ageing as well as in sciatica and clinically defined degenerative conditions, targeting mast cell function may be a viable conservative treatment option for the ageing IVD in health and disease. This review discusses the possible involvement of mast cells in IVD health and disease, and the rationale for the use of mast cell stabilizers such as ketotifen as potential treatment options for conditions affecting IVD integrity. Such mast cell targeting treatments may be considered alone or in combination with other molecules such as specific proteinase inhibitors impacting proteinases known to be present in the affected tissues, such as MMP-3 and HTRA1. Thus, a multicomponent approach in such treatments may provide effectiveness in inhibiting progressive loss of IVD integrity and function in chronic degenerative conditions or adverse outcomes due to non-resorption of extruded nucleus pulposus in sciatica.

## Linked entities

- **Proteins:** MMP3 (matrix metallopeptidase 3), HTRA1 (HtrA serine peptidase 1)
- **Chemicals:** ketotifen (PubChem CID 3827)
- **Diseases:** sciatica (MONDO:0024333)

## Full-text entities

- **Genes:** HTRA1 (HtrA serine peptidase 1) [NCBI Gene 5654] {aka ARMD7, CADASIL2, CARASIL, CARASIL2, HtrA, L56}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}
- **Diseases:** sciatica (MESH:D012585), asthma (MESH:D001249), allergies (MESH:D004342), inflammatory (MESH:D007249)
- **Chemicals:** ketotifen (MESH:D007665)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13026124/full.md

## References

238 references — full list in the complete paper: https://tomesphere.com/paper/PMC13026124/full.md

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Source: https://tomesphere.com/paper/PMC13026124