{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:41:52Z","timestamp":1790203312462,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,9,28]],"date-time":"2017-09-28T00:00:00Z","timestamp":1506556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001858","name":"VINNOVA","doi-asserted-by":"publisher","award":["2012\u201004409"],"award-info":[{"award-number":["2012\u201004409"]}],"id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR056802"],"award-info":[{"award-number":["AR056802"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["K2014\u20107X\u201022506\u201001\u20103"],"award-info":[{"award-number":["K2014\u20107X\u201022506\u201001\u20103"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>Currently, there are no medications available to treat aseptic loosening of orthopedic implants. Using osteoprotegerin fusion protein (OPG\u2010Fc), we previously blocked instability\u2010induced osteoclast differentiation and peri\u2010prosthetic osteolysis. Wnt\/\u03b2\u2010catenin signaling, which regulates OPG secretion from osteoblasts, also modulates the bone tissue response to mechanical loading. We hypothesized that activating Wnt\/\u03b2\u2010catenin signaling by inhibiting glycogen synthase kinase\u20103\u03b2 (GSK\u20103\u03b2) would reduce instability\u2010induced bone loss through regulation of both osteoblast and osteoclast differentiation. We examined effects of GSK\u20103\u03b2 inhibition on regulation of RANKL and OPG in a rat model of mechanical instability\u2010induced peri\u2010implant osteolysis. The rats were treated daily with a GSK\u20103\u03b2 inhibitor, AR28 (20\u2009mg\/kg bw), for up to 5 days. Bone tissue and blood serum were assessed by qRT\u2010PCR, immunohistochemistry, and ELISA on days 3 and 5, and by micro\u2010CT on day 5. After 3 days of treatment with AR28, mRNA levels of \u03b2\u2010catenin, Runx2, Osterix, Col1\u03b11, and ALP were increased leading to higher osteoblast numbers compared to vehicle\u2010treated animals. BMP\u20102 and Wnt16 mRNA levels were downregulated by mechanical instability and this was rescued by GSK\u20103\u03b2 inhibition. Osteoclast numbers were decreased significantly after 3 days of GSK\u20103\u03b2 inhibition, which correlated with enhanced OPG mRNA expression. This was accompanied by decreased serum levels of TRAP5b on days 3 and 5. Treatment with AR28 upregulated osteoblast differentiation, while osteoclastogenesis was blunted, leading to increased bone mass by day 5. These data suggest that GSK\u20103\u03b2 inactivation suppresses osteolysis through regulating both osteoblast and osteoclast differentiation in a rat model of instability\u2010induced osteolysis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26111","type":"journal-article","created":{"date-parts":[[2017,7,21]],"date-time":"2017-07-21T07:12:47Z","timestamp":1500621167000},"page":"2398-2408","source":"Crossref","is-referenced-by-count":44,"title":["GSK\u20103\u03b2 inhibition suppresses instability\u2010induced osteolysis by a dual action on osteoblast and osteoclast differentiation"],"prefix":"10.1002","volume":"233","author":[{"given":"Mehdi","family":"Amirhosseini","sequence":"first","affiliation":[{"name":"Division of Cell Biology, Department of Clinical and Experimental Medicine Link\u00f6ping University Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rune V.","family":"Madsen","sequence":"additional","affiliation":[{"name":"Adult Reconstruction and Joint Replacement Service Hospital for Special Surgery New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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