Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Matrix metalloproteinase-7–dependent release of tumor necrosis factor-α in a model of herniated disc resorption
Hirotaka Haro, … , Dan M. Spengler, Lynn M. Matrisian
Hirotaka Haro, … , Dan M. Spengler, Lynn M. Matrisian
Published January 15, 2000
Citation Information: J Clin Invest. 2000;105(2):143-150. https://doi.org/10.1172/JCI7091.
View: Text | PDF
Article

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

  • Text
  • PDF
Abstract

Herniated disc (HD), one of the major causes of low back pain, is often resolved spontaneously without surgical intervention. Resorption is associated with a marked increase in infiltrating macrophages, and the matrix metalloproteinases (MMP) MMP-3 and MMP-7 have been implicated in this phenomenon. We developed a murine organ culture model in which intact intervertebral discs were cocultured with peritoneal macrophages to investigate the role of MMPs in HD resorption. Using macrophages isolated from MMP-null mice, we report that macrophage-produced MMP-7 was required for proteoglycan degradation, loss of wet weight, and macrophage infiltration of cocultured discs. The inability of MMP-7–deficient macrophages to infiltrate discs could not be attributed to a defect in macrophage migration. MMP-7 was required for the release of the cytokine TNF-α from peritoneal macrophages. The generation of soluble TNF-α was essential for the induction of MMP-3 in disc cocultures, which in turn is required for the generation of a macrophage chemoattractant and subsequent macrophage infiltration. TNF-α release from macrophages was necessary but insufficient for disc resorption, which required macrophage infiltration. We conclude that there is extensive communication between macrophages and chondrocytes in HD resorption and that an essential component of this communication is the requirement for MMPs to release soluble bioactive factors.

Authors

Hirotaka Haro, Howard C. Crawford, Barbara Fingleton, Kenichi Shinomiya, Dan M. Spengler, Lynn M. Matrisian

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Quantitative analysis of macrophage migratory activity. Wild-type (wt), ...
Quantitative analysis of macrophage migratory activity. Wild-type (wt), MMP-3–null (3–), and MMP-7–null (7–) macrophages were placed in the top well of a modified Boyden chamber, and the number of macrophages migrating through the filter was counted in 6 random ×400 high-power fields for each well. (a) BSA (200 μg/mL) in DMEM or FBS (10%) in DMEM was placed in the lower chamber. (b) Conditioned medium from intervertebral discs from wild-type mice (disc) or discs cocultured with wild-type macrophages (mφ/disc) was placed in the lower chamber. Data from 2 experiments performed in triplicate were analyzed with the Mann-Whitney test and presented as mean ± SD. *Statistically significant differences (P < 0.05) compared with control medium.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts