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

• DOI: 10.1073/pnas.95.23.13453
• Publication Date: 2002-07-26T14:32:33Z
• Authors: Paul Saftig; Ernst Hunziker; Olaf Wehmeyer; Sheila Jones; Alan Boyde; Winfried Rommersk...; Jörg Detlev Moritz; Peter Schu; Kurt von Figura
• Keywords: Cathepsin K; Osteopetrosis; Osteosclerosis; Bone remodeling

Cathepsin K is a recently identified lysosomal cysteine proteinase. It abundant in osteoclasts, where it believed to play vital role the resorption and remodeling of bone. Pycnodysostosis rare inherited osteochondrodysplasia that caused by mutations cathepsin-K gene, characterized osteosclerosis, short stature, acroosteolysis distal phalanges. With view delineating cathepsin bone resorption, we generated mice with targeted disruption this Cathepsin-K-deficient survive are fertile, but display an osteopetrotic phenotype excessive trabeculation bone-marrow space. osteoclasts manifested modified ultrastructural appearance: their resorptive surface was poorly defined broad demineralized matrix fringe containing undigested fine collagen fibrils; ruffled borders lacked crystal-like inclusions, they were devoid collagen-fibril-containing cytoplasmic vacuoles. Assaying activity cathepsin-K-deficient vitro revealed function be severely impaired, which supports contention major importance remodeling.