{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:01:31Z","timestamp":1772118091837,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2008,1,31]],"date-time":"2008-01-31T00:00:00Z","timestamp":1201737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cathepsin K is believed to have an eminent role in the pathologic resorption of bone. However, several studies have shown that other proteinases also participate in this process. In order to clarify the contribution of cathepsin K to the destruction of arthritic bone, we applied the human tumor necrosis factor (hTNF)\u2013transgenic mouse model, in which severe polyarthritis characterized by strong osteoclast\u2010mediated bone destruction develops spontaneously.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Arthritis was evaluated in hTNF\u2010transgenic mice that were either wild\u2010type for cathepsin K (CK\n                      <jats:sup>+\/+<\/jats:sup>\n                      ), heterozygous for cathepsin K (CK\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                      ), or deficient in cathepsin K (CK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ). Arthritic knee joints were prepared for standard histologic assessment aimed at establishing a semiquantitative score for joint destruction and quantification of the area of bone erosion. Additionally, microfocal computed tomography was performed to visualize bone destruction in mice with the different CK genotypes. CK\n                      <jats:sup>+\/+<\/jats:sup>\n                      and CK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      osteoclasts were generated in vitro, and their proteinase expression profiles were compared by complementary DNA array analysis, real\u2010time polymerase chain reaction, and activity assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Although the area of bone erosion was significantly reduced in hTNF\u2010transgenic CK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, the absence of cathepsin K did not completely protect against inflammatory bone lesions. Several matrix metalloproteinases (MMPs) and cathepsins were expressed by in vitro\u2013generated CK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      osteoclasts, without marked differences from CK\n                      <jats:sup>+\/+<\/jats:sup>\n                      osteoclasts. MMP activity was detected in CK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      osteoclasts, and MMP\u201014 was localized by immunohistochemistry in inflammatory bone erosions in hTNF\u2010transgenic CK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, suggesting MMPs as potential contributors to bone destruction. Additionally, we detected a reduction in osteoclast formation in cathepsin K\u2013deficient mice, both in vitro and in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results of our experiments raise doubts about a crucial role of cathepsin K in arthritic bone destruction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.23224","type":"journal-article","created":{"date-parts":[[2008,1,31]],"date-time":"2008-01-31T14:51:40Z","timestamp":1201791100000},"page":"422-434","source":"Crossref","is-referenced-by-count":30,"title":["Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor\u2013transgenic 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