{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:23:13Z","timestamp":1791375793634,"version":"4.3.1"},"reference-count":37,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,11,10]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>in vitro<\/jats:italic>\n                    revealed this function to be severely impaired, which supports the contention that cathepsin K is of major importance in bone remodeling.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.23.13453","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:32:33Z","timestamp":1027679553000},"page":"13453-13458","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":785,"title":["Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice"],"prefix":"10.1073","volume":"95","author":[{"given":"Paul","family":"Saftig","sequence":"first","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"Hunziker","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Wehmeyer","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Jones","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Boyde","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Rommerskirch","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg Detlev","family":"Moritz","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Schu","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, Robert-Koch..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"von Figura","sequence":"additional","affiliation":[{"name":"Zentrum Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universit\u00e4t G\u00f6ttingen, Gosslerstrasse 12 d, 37073 G\u00f6ttingen, Germany; Universit\u00e4t Bern, M.E. M\u00fcller-Institut f\u00fcr Biomechanik, Murtenstrasse 35, CH-3010 Bern, Switzerland; Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom; Institut f\u00fcr Biochemie, Universit\u00e4t Jena, L\u00f6bder Strasse 3, 07740 Jena, Germany; and Zentrum Radiologie, Universit\u00e4t G\u00f6ttingen, 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