{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:06Z","timestamp":1786978026170,"version":"build-2736575974"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T00:00:00Z","timestamp":1508716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Cathepsin K (CatK) is a widely expressed cysteine protease that has gained attention because of its enzymatic and non\u2010enzymatic functions in signalling. Here, we examined whether CatK\u2010deficiency (CatK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) would mitigate injury\u2010related skeletal muscle remodelling and fibrosis in mice, with a special focus on inflammation and muscle cell apoptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cardiotoxin (CTX, 20\u00a0\u03bcM\/200\u00a0\u03bcL) was injected into the left gastrocnemius muscle of male wild\u2010type (CatK\n                      <jats:sup>+\/+<\/jats:sup>\n                      ) and CatK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, and the mice were processed for morphological and biochemical studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      On post\u2010injection Day 14, CatK deletion ameliorated muscle interstitial fibrosis and remodelling and performance. At an early time point (Day 3), CatK\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      reduced the lesion macrophage and leucocyte contents and cell apoptosis, the mRNA levels of monocyte chemoattractant protein\u20101, toll\u2010like receptor\u20102 and toll\u2010like receptor\u20104, and the gelatinolytic activity related to matrix metalloproteinase\u20102\/\u20109. CatK deletion also restored the protein levels of caspase\u20103 and cleaved caspase\u20108 and the ratio of the BAX to the Bcl\u20102. Moreover, CatK deficiency protected muscle fibre laminin and desmin disorder in response to CTX injury. These beneficial muscle effects were mimicked by CatK\u2010specific inhibitor treatment.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments demonstrated that pharmacological CatK inhibition reduced the apoptosis of C2C12 mouse myoblasts and the levels of BAX and caspase\u20103 proteins induced by CTX.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results demonstrate that CatK plays an essential role in skeletal muscle loss and fibrosis in response to CTX injury, possibly via a reduction of inflammation and cell apoptosis, suggesting a novel therapeutic strategy for the control of skeletal muscle diseases by regulating CatK activity.<\/jats:p>\n                  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