Localization of matrix metalloproteinase 9 (92-kilodalton gelatinase/type IV collagenase = gelatinase B) in osteoclasts: Implications for bone resorption

Y. Okada, K. Naka, K. Kawamura, T. Matsumoto, I. Nakanishi, N. Fujimoto, H. Sato, M. Seiki

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BACKGROUND: Matrix metalloproteinase 9 (MMP-9, 92-kD gelatinase/type IV collagenase = gelatinase B) is a member of the MMP gene family and implicated in tissue destruction in the various pathophysiologic conditions. Our previous study showed that MMP-9 purified from human fibrosarcoma cells can cleave the cross-link-containing NH2-terminal telopeptides of the α2 chain of type I collagen and collagen types III, IV, and V as well as gelatins. EXPERIMENTAL DESIGN: To investigate the role of MMP-9 in bone resorption we have examined its localization in the human bone tissues by immunohistochemistry and in situ hybridization. The enzymic properties were also biochemically studied. RESULTS: Immunohistochemistry using monoclonal antibodies against MMP-1 (interstitial collagenase), MMP-2 (72-kD gelatinase/type IV collagenase = gelatinase A), MMP-3 (stromelysin-1), MMP- 9, and tissue inhibitor of metalloproteinases-1 demonstrated that MMP-9 is localized exclusively in osteoclasts of the bone tissues from normal subjects and patients with rheumatoid arthritis or metastatic carcinoma whereas some osteoclasts are also labeled by anti-(MMP-1) antibody. Northern blot and in situ hybridizations of rheumatoid bone tissues using a RNA probe for MMP-9 exhibited strong signals for the mRNA within osteoclasts. MMP-9 depolymerized acid-insoluble polymers of type I collagen and digested collagen fibrils in the demineralized bone. The gelatinolytic activity of the proteinase was optimal at pH 7.5, but 50 to 80% of the full activity was retained at pH 5.5 to 6.0. It was also 90% active in the presence of 100 mM Ca2+. Degradation of acid-soluble and -insoluble type I collagens by MMP-9 was enhanced at higher concentrations of Ca2+. The zymogen of MMP-9 was activated up to Å85% of full activity by incubation at pH 2.3. CONCLUSIONS: These results demonstrate that MMP-9 is produced by osteoclasts in the human bone tissues and suggest that it can degrade bone collagens in concert with MMP-1 and cysteine proteinases in the subosteoclastic microenvironment. This proteinase may play a role in the normal bone remodeling and pathologic bone resorption in the human diseases.

Original languageEnglish
Pages (from-to)311-322
Number of pages12
JournalLaboratory Investigation
Issue number3
Publication statusPublished - 1995 Jan 1


  • Extracellular matrix degradation
  • biochemical characterization
  • bone remodeling
  • immunolocalization
  • in situ hybridization
  • tissue inhibitor of metalloproteinases- 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology


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