{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:34:01Z","timestamp":1782974041370,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005694","name":"Hori Sciences and Arts Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Periprosthetic osteolysis induced by wear debris remains a leading cause of aseptic loosening after joint arthroplasty, with no established pharmacological treatment. We investigated an anti\u2010sclerostin antibody (Ab\u2010Scl) and elucidated its mechanism of action in cobalt\u2010chromium (CoCr) particle\u2010induced osteolysis. Tartrate\u2010resistant acid phosphatase (TRAP)\u2010tdTomato mice with labeled mature osteoclasts (mOCs) were used. CoCr particles were applied to the calvarial bone, with or without Ab\u2010Scl administration. Intravital two\u2010photon bone imaging, microcomputed tomography (\u03bcCT), and histological and immunohistochemical analyses were performed to evaluate osteolysis, osteoclast activity, and \u03b2\u2010catenin expression. In vitro assays using RAW264.7\u2010derived osteoclast\u2010like cells were conducted to investigate downstream signaling pathways. \u03bcCT analysis revealed that CoCr particles reduced the bone volume\u2013to\u2013tissue volume fraction and trabecular thickness while increasing trabecular separation and the structural model index; conversely, Ab\u2010Scl significantly attenuated osteolytic changes. Histological analysis showed that CoCr exposure increased the eroded surface area and number of TRAP\u2010positive osteoclasts, both of which were significantly decreased by Ab\u2010Scl. Immunohistochemistry demonstrated that CoCr exposure suppressed \u03b2\u2010catenin expression on the bone surface, which was restored by Ab\u2010Scl. Intravital two\u2010photon microscopy revealed that CoCr particles reduced mOC motility and increased the acidic resorptive area, whereas Ab\u2010Scl reversed these changes, enhancing motility and suppressing bone resorption. In vitro, RSPO2 enhanced osteoclastic bone resorption, pit formation, and Pyk2 phosphorylation, which were suppressed by PF\u2010562271. Ab\u2010Scl modulated osteoclast function through Wnt\/\u03b2\u2010catenin\u2010related mechanisms, potentially involving Pyk2\u2010related pathways, thereby suppressing CoCr particle\u2010induced osteolysis. These findings suggest that Ab\u2010Scl is a promising pharmacological strategy for preventing aseptic loosening following joint arthroplasty.<\/jats:p>","DOI":"10.1002\/jor.70231","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:30:23Z","timestamp":1780626623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Sclerostin Protected Against Particle\u2010Induced Osteolysis via Activation of Wnt Signaling and Suppression of Osteoclast Function"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2286-3045","authenticated-orcid":false,"given":"Hiroaki","family":"Ido","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9279-8301","authenticated-orcid":false,"given":"Yasuhiko","family":"Takegami","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Osawa","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5182-6369","authenticated-orcid":false,"given":"Hiroto","family":"Funahashi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Otaka","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimihiro","family":"Oono","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Wake","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Molecular Cell Biology Nagoya University Graduate School of Medicine Nagoya Aichi Japan"},{"name":"Division of Multicellular Circuit Dynamics, National Institute for Physiological Sciences National Institute of Natural Sciences Okazaki Aichi Japan"},{"name":"School of Medical Sciences UNSW Sydney Sydney Australia"},{"name":"Organization for Advanced and Integrated Research Kobe University Kobe Japan"},{"name":"Core Research for Evolutional Science and Technology Japan Science and Technology Agency Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Imagama","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Nagoya University Graduate School of Medicine, 65 Tsurumai\u2010cho Nagoya Showa\u2010ku Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.170990"},{"issue":"5","key":"e_1_2_10_3_1","first-page":"1130","article-title":"Primary Total Hip Arthroplasty With a Porous\u2010Coated Acetabular Component: A Concise Follow\u2010Up, at a Minimum of Twenty Years, of Previous Reports","volume":"91","author":"Della Valle C. 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