{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:55:10Z","timestamp":1777398910248,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>We aimed to investigate whether post\u2010traumatic osteoarthritis (PTOA) progression is appropriately represented by a PTOA mouse model using a unique climbing cage to add mechanical loading after anterior cruciate ligament (ACL) transection and to determine how Hedgehog signaling inhibition prevents PTOA progression by observing time\u2010dependent morphological changes. This controlled laboratory study histologically compared mice with surgically\u2010induced ACL transection (ACLT) and those with voluntary increased activity in a climbing cage from 1 week postoperatively (ACLT\u2009+\u2009climbing). We generated conditional knockout (cKO) mice with a deleted Smoothened (Smo) gene. Time\u2010dependent histopathological, immunohistochemical, and gene expression analyses were performed. The ACLT\u2009+\u2009climbing group showed more severe cartilage defects and massive osteophyte formation than the ACLT group. Smo deletion significantly suppressed PTOA progression. The time\u2010dependent assessment revealed cartilaginous processes of equivalent size at the posterior tibial margin in the Smo cKO and control mice at 4 weeks postoperatively. However, at 8 weeks postoperatively, mature ossifying lesions were detected in the controls but not in Smo cKO mice. In the articular cartilage, ADAMTS5 and RUNX2 expression were observed in hypertrophic chondrocytes near the defective cartilage in controls but not in Smo cKO mice. Climbing exercise after ACLT accelerated PTOA progression more severely not only through increasing joint instability induced by ACLT but also through mechanical loading force induced by climbing exercise. Hedgehog signaling inhibition attenuated PTOA progression by suppressing chondrocyte hypertrophy induced by mechanical loads, to which ACL\u2010deficient athletes are usually exposed. Thus, Hedgehog signaling inhibition may be a therapeutic option to prevent arthritic changes in athletes. \u00a9 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:609\u2013619, 2020<\/jats:p>","DOI":"10.1002\/jor.24494","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T07:52:41Z","timestamp":1571039561000},"page":"609-619","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Attenuation of Post\u2010Traumatic Osteoarthritis After Anterior Cruciate Ligament Injury Via Inhibition of Hedgehog Signaling"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-8262","authenticated-orcid":false,"given":"Shinichiro","family":"Takada","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery University of Occupational and Environmental Health 1\u20101 Iseigaoka Yahatanishui\u2010ku Kitakyushu Fukuoka 807\u20108555 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