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Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice
Open accessAbstract
Cathepsin K is a recently identified lysosomal cysteine proteinase. It is abundant in osteoclasts, where it is believed to play a vital role in the resorption and remodeling of bone. Pycnodysostosis is a rare inherited osteochondrodysplasia that is caused by mutations of the cathepsin-K gene, characterized by osteosclerosis, short stature, and acroosteolysis of the distal phalanges. With a view to delineating the role of cathepsin K in bone resorption, we generated mice with a targeted disruption of this proteinase. Cathepsin-K-deficient mice survive and are fertile, but display an osteopetrotic phenotype with excessive trabeculation of the bone-marrow space. Cathepsin-K-deficient osteoclasts manifested a modified ultrastructural appearance: their resorptive surface was poorly defined with a broad demineralized matrix fringe containing undigested fine collagen fibrils; their ruffled borders lacked crystal-like inclusions, and they were devoid of collagen-fibril-containing cytoplasmic vacuoles. Assaying the resorptive activity of cathepsin-K-deficient osteoclasts in vitro revealed this function to be severely impaired, which supports the contention that cathepsin K is of major importance in bone remodeling.
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Metadata
- Authors
- Saftig, P., Hunziker, E., Wehmeyer, O., Jones, S., Boyde, A., Rommerskirch, W., Moritz, J. D., Schu, P., & von Figura, K.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-11-10
- Volume
- 95
- Issue
- 23
- Pages
- 13453-13458
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2025062557
- Cited by
- 913
- References
- 2
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- green
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