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Extracellular Matrix Degradation pp 23–51Cite as

Role of Cysteine Cathepsins in Extracellular Proteolysis

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Part of the book series: Biology of Extracellular Matrix ((BEM,volume 2))

Abstract

Cysteine cathepsins are lysosomal proteases with housekeeping as well as highly specialized functions. Although their activities are optimal at lysosomal acidic and reducing conditions, cathepsins can significantly contribute to the degradation of the extracellular matrix. This may happen under physiological conditions as in cathepsin K-mediated bone resorption or under pathological conditions. Extracellular matrix degradation can occur extracellularly by the secretion of cathepsins or intracellularly following the endocytosis of matrix material. Under physiological conditions, the extracellular matrix is safeguarded against cathepsin activities by its neutral pH, oxidative environment, and high levels of potent endogenous cathepsin inhibitors. However, these barriers can be overcome by pericellular acidification and pathophysiologically reduced anticathepsin concentrations. Whereas matrix metalloproteases are primarily responsible for the homeostasis of the extracellular matrix, cysteine proteases contribute to its destruction under disease conditions. The development of cathepsin inhibitors as anti matrix-degrading drugs appears to be a successful strategy.

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Acknowledgments

Support: DB: Canada Research Award and Canadian Institutes of Health Research grants: MOP 86586, MOP 6447, and 89974.

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  1. Department of Oral and Biological Sciences, University of British Columbia, 2100 Wesbrook Mall, Vancouver, BC, Canada, V6T 1Z3

    Dieter Brömme & Susan Wilson

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  1. Dieter Brömme
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Correspondence to Dieter Brömme .

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  1. Center for Lung Biology, University of Washington, Mercer Street 815, Seattle, 98109, Washington, USA

    William C. Parks

  2. School of Medicine, Dept. Cell Biology & Physiology, Washington University, S. Euclid Avenue 660, St. Louis, 63110, Missouri, USA

    Robert P. Mecham

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Brömme, D., Wilson, S. (2011). Role of Cysteine Cathepsins in Extracellular Proteolysis. In: Parks, W., Mecham, R. (eds) Extracellular Matrix Degradation. Biology of Extracellular Matrix, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16861-1_2

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