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Updated: Oct 18, 2026

A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.
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A Proinflammatory, Degenerative Organ Culture Model to Simulate Early-Stage Intervertebral Disc Disease.

Published on: February 14, 2021

Matrix metalloproteinase-7-dependent release of tumor necrosis factor-alpha in a model of herniated disc resorption

H Haro1, H C Crawford, B Fingleton

  • 1Department of Orthopaedics and Rehabilitation, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

The Journal of Clinical Investigation
|January 22, 2000
PubMed

Insights

Matrix metalloproteinase-7 (MMP-7) is crucial for herniated disc (HD) resorption by macrophages. MMP-7 facilitates proteoglycan degradation and the release of TNF-alpha, essential for macrophage infiltration and disc healing.

Area of Science:

  • Biochemistry
  • Immunology
  • Orthopedics

Background:

  • Herniated disc (HD) is a common cause of low back pain, often resolving spontaneously.
  • Macrophage infiltration and matrix metalloproteinases (MMPs) are implicated in HD resorption.

Purpose of the Study:

  • To investigate the role of MMPs, specifically MMP-7, in the resorption of herniated discs using a murine organ culture model.

Main Methods:

  • Coculturing intact intervertebral discs with peritoneal macrophages from wild-type and MMP-null mice.
  • Assessing proteoglycan degradation, wet weight loss, macrophage infiltration, and cytokine release (TNF-alpha).

Main Results:

  • Macrophage-produced MMP-7 is essential for proteoglycan degradation, wet weight loss, and macrophage infiltration of discs.
  • MMP-7 is required for TNF-alpha release from macrophages, which induces MMP-3 in disc cells.
  • TNF-alpha and subsequent MMP-3 are necessary for generating macrophage chemoattractants and infiltration.

Conclusions:

  • Macrophage-derived MMP-7 plays a critical role in herniated disc resorption.
  • Effective disc resorption requires communication between macrophages and chondrocytes, mediated by MMPs releasing soluble factors like TNF-alpha.

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