{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:58:24Z","timestamp":1788346704434,"version":"build-2803163510"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":2206,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T00:00:00Z","timestamp":1522627200000},"content-version":"vor","delay-in-days":66,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Patients with anterior cruciate ligament (ACL) rupture are two times as likely to develop posttraumatic osteoarthritis (PTOA). Annually, there are \u223c900,000 knee injuries in the United States, which account for \u223c12% of all osteoarthritis (OA) cases. PTOA leads to reduced physical activity, deconditioning of the musculoskeletal system, and in severe cases requires joint replacement to restore function. Therefore, treatments that would prevent cartilage degradation post-injury would provide attractive alternatives to surgery. Sclerostin (Sost), a Wnt antagonist and a potent negative regulator of bone formation, has recently been implicated in regulating chondrocyte function in OA. To determine whether elevated levels of Sost play a protective role in PTOA, we examined the progression of OA using a noninvasive tibial compression overload model in SOST transgenic (SOSTTG) and knockout (Sost-\/-) mice. Here we report that SOSTTG mice develop moderate OA and display significantly less advanced PTOA phenotype at 16 weeks post-injury compared with wild-type (WT) controls and Sost-\/-. In addition, SOSTTG built \u223c50% and \u223c65% less osteophyte volume than WT and Sost-\/-, respectively. Quantification of metalloproteinase (MMP) activity showed that SOSTTG had \u223c2-fold less MMP activation than WT or Sost-\/-, and this was supported by a significant reduction in MMP2\/3 protein levels, suggesting that elevated levels of SOST inhibit the activity of proteolytic enzymes known to degrade articular cartilage matrix. Furthermore, intra-articular administration of recombinant Sost protein, immediately post-injury, also significantly decreased MMP activity levels relative to PBS-treated controls, and Sost activation in response to injury was TNF\u03b1 and NF-\u03baB dependent. These results provide in vivo evidence that sclerostin functions as a protective molecule immediately after joint injury to prevent cartilage degradation. \u00a9 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.3397","type":"journal-article","created":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T14:25:35Z","timestamp":1516976735000},"page":"1105-1113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["SOST\/Sclerostin Improves Posttraumatic Osteoarthritis and Inhibits MMP2\/3 Expression After Injury"],"prefix":"10.1093","volume":"33","author":[{"given":"Jiun C","family":"Chang","sequence":"first","affiliation":[{"name":"University of California at MercedSchool of Natural SciencesMercedCAUSA"},{"name":"Lawrence Livermore National LaboratoriesPhysical and Life Sciences DirectorateLivermoreCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blaine A","family":"Christiansen","sequence":"additional","affiliation":[{"name":"University of California Davis Medical CenterSacramentoCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa K","family":"Murugesh","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National LaboratoriesPhysical and Life Sciences DirectorateLivermoreCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimy","family":"Sebastian","sequence":"additional","affiliation":[{"name":"University of California at MercedSchool of Natural SciencesMercedCAUSA"},{"name":"Lawrence Livermore National LaboratoriesPhysical and Life Sciences DirectorateLivermoreCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R","family":"Hum","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National LaboratoriesPhysical and Life Sciences DirectorateLivermoreCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M","family":"Collette","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National LaboratoriesPhysical and Life Sciences DirectorateLivermoreCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Hatsell","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris N","family":"Economides","sequence":"additional","affiliation":[{"name":"Regeneron PharmaceuticalsTarrytownNYUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig D","family":"Blanchette","sequence":"additional","affiliation":[{"name":"Lawrence Livermore National LaboratoriesPhysical and Life Sciences DirectorateLivermoreCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela G","family":"Loots","sequence":"additional","affiliation":[{"name":"University of California at MercedSchool of Natural SciencesMercedCAUSA"},{"name":"Lawrence Livermore National LaboratoriesPhysical and Life Sciences DirectorateLivermoreCAUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,1,26]]},"reference":[{"issue":"7","key":"2024021014275080000_jbmr3397-bib-0001","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.joca.2012.04.014","article-title":"Musculoskeletal changes following non-invasive knee injury using a novel mouse model of post-traumatic osteoarthritis","volume":"20","author":"Christiansen","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"issue":"1","key":"2024021014275080000_jbmr3397-bib-0002","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.otsr.2013.12.010","article-title":"Arthrosis of the knee in chronic anterior laxity","volume":"100","author":"Dejour","year":"2014","journal-title":"Orthop Traumatol Surg Res"},{"issue":"5","key":"2024021014275080000_jbmr3397-bib-0003","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1002\/art.21813","article-title":"Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide","volume":"54","author":"Loeser","year":"2006","journal-title":"Arthritis Rheum"},{"issue":"10","key":"2024021014275080000_jbmr3397-bib-0004","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1177\/0363546507307396","article-title":"The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis","volume":"35","author":"Lohmander","year":"2007","journal-title":"Am J Sports Med"},{"issue":"4","key":"2024021014275080000_jbmr3397-bib-0005","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/ar3113","article-title":"New developments in osteoarthritis. 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