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

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.

Pubmed ID: 9811821


  • Saftig P
  • Hunziker E
  • Wehmeyer O
  • Jones S
  • Boyde A
  • Rommerskirch W
  • Moritz JD
  • Schu P
  • von Figura K


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

November 10, 1998

Associated Grants


Mesh Terms

  • Animals
  • Bone Resorption
  • Cathepsin K
  • Cathepsins
  • Disease Models, Animal
  • Mice
  • Mice, Knockout
  • Osteoclasts
  • Osteopetrosis