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Lab Invest. 1995 Mar;72(3):311-22.

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

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Department of Pathology, School of Medicine, Kanazawa University, Japan.



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 NH(2)-terminal telopeptides of the alpha 2 chain of type I collagen and collagen types III, IV, and V as well as gelatins.


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.


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 approximately 85% of full activity by incubation at pH 2.3.


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.

[Indexed for MEDLINE]

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