Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice.

Abstract

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.

• Authors: P Saftig, E Hunziker, O Wehmeyer, S Jones, A Boyde, W Rommerskirch, J D Moritz, P Schu, K von Figura
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 23 Pg. 13453-8 (Nov 10 1998) ISSN: 0027-8424 [Print] United States
• PMID: 9811821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cathepsins
• Cathepsin K
• Ctsk protein, mouse

Topics

• Animals
• Bone Resorption (metabolism)
• Cathepsin K
• Cathepsins (deficiency, genetics)
• Disease Models, Animal
• Mice
• Mice, Knockout
• Osteoclasts (metabolism)
• Osteopetrosis (genetics, metabolism)