Degradation of collagen in the bone-resorbing compartment underlying the osteoclast involves both cysteine-proteinases and matrix metalloproteinases

Authors

  • Vincent Everts,

    Corresponding author
    1. Experimental Oral Biology Group, Laboratory of Cell Biology and Histology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam
    2. Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), the Netherlands
    • Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), the Netherlands
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  • Jean-Marie Delaissé,

    1. Laboratoire de Chimie Physiologique (Connective Tissue Group), Université de Louvain and International Institute of Cellular and Molecular Pathology, B-1200 Bruxelles, Belgium
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  • Wolf Korper,

    1. Experimental Oral Biology Group, Laboratory of Cell Biology and Histology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam
    2. Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), the Netherlands
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  • Anneke Niehof,

    1. Experimental Oral Biology Group, Laboratory of Cell Biology and Histology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam
    2. Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), the Netherlands
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  • Gilbert Vaes,

    1. Laboratoire de Chimie Physiologique (Connective Tissue Group), Université de Louvain and International Institute of Cellular and Molecular Pathology, B-1200 Bruxelles, Belgium
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  • Wouter Beertsen

    1. Experimental Oral Biology Group, Laboratory of Cell Biology and Histology, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam
    2. Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), the Netherlands
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Abstract

The site of action of cysteine-proteinases (CPs) and matrix metalloproteinases (MMPs) in the degradation of bone collagen by osteoclasts was investigated by evaluating the effects of the CP-inhibitor trans-epoxy-succinyl-L-leucylamido (4-guanidino)-butane (E-64) and the MMP-inhibitor N-(3-N-benzyloxycarbonyl amino-1-R-carboxypropyl)-L-leucyl-O-methyl-L-tyrosine N-methylamide (Cl-1) in an in vitro model system of PTH-stimulated mouse calvaria. In the presence of each of the two inhibitors a large area of collagen free of mineral crystallites was seen adjacent to the ruffled border of the osteoclasts. Following a culture period of 24 h this area proved to be about 10 times larger in inhibitor-treated explants than in controls. Moreover the percentage of osteoclasts in close contact with such demineralized bone areas appeared to be significantly higher in inhibitor-treated explants than in control specimens (60% and 5%, respectively). These effects were not apparent when the osteoclastic activity was inhibited with calcitonin. No significant differences were found between the effects of the two inhibitors, E-64 and Cl-1. Our observations indicate that under the influence of inhibitors of MMPs and CPs demineralization of bone by osteoclasts proceeded up to a certain point whereas matrix degradation was strongly inhibited. It is concluded that within the osteoclastic resorption lacuna both CPs and MMPs participate in the degradation of the collagenous bone matrix.

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