{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:03:38Z","timestamp":1772726618703,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515111115"],"award-info":[{"award-number":["2022A1515111115"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515110698"],"award-info":[{"award-number":["2021A1515110698"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Orthopaedic Surgery"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to investigate the role of Denosumab and its downstream target ST18 in wear particle\u2010induced macrophage inflammation and osteolysis, and to explore the underlying mechanisms involved in aseptic loosening (AL) of prosthetic joints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Macrophages were stimulated with titanium particles (TiPs), and inflammatory responses were assessed using qRT\u2010PCR, western blot, flow cytometry, and immunohistochemistry. Denosumab's effects on inflammation and osteolysis were evaluated with the same approaches. Potential targets of Denosumab were screened via online databases and validated by qRT\u2010PCR and western blot. ST18 was modulated in macrophages using lentiviral overexpression and knockdown systems. A mouse calvarial model of TiPs\u2010induced osteolysis was established, and the roles of Denosumab and ST18 were examined in\u00a0vivo using micro\u2010CT, H&amp;E staining, and tartrate\u2010resistant acid phosphatase (TRACP) staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Denosumab suppressed TiPs\u2010induced macrophage inflammation by inhibiting NF\u2010\u03baB signaling and M1 polarization. We identified ST18 as a direct target of Denosumab, whose expression was upregulated by TiPs but downregulated by Denosumab. Lentivirus\u2010mediated ST18 knockdown markedly attenuated TiPs\u2010induced inflammation, whereas ST18 overexpression exacerbated it. Further analysis revealed that ST18 interacts with PARP1. In\u00a0vivo, Denosumab significantly alleviated TiPs\u2010induced osteolysis in mouse calvaria, an effect that was reversed by ST18 overexpression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Denosumab attenuates TiPs\u2010induced macrophage activation and osteolysis through suppression of the NF\u2010\u03baB pathway and M1 polarization, with ST18 serving as a key mediator. These findings highlight Denosumab as a promising therapeutic candidate for the prevention of prosthesis\u2010related aseptic loosening.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/os.70211","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:20:11Z","timestamp":1767054011000},"page":"322-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Denosumab Regulates Titanium Particles\u2010Induced Macrophages Inflammation and Osteolysis by Targeting the\n                    <scp>ST18<\/scp>\n                    \/\n                    <scp>PARP1<\/scp>\n                    Interaction"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4415-9406","authenticated-orcid":false,"given":"Zhipeng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jichao","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Sun Yat\u2010Sen Memorial Hospital, Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.170990"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17453674.2019.1597062"},{"issue":"17","key":"e_1_2_12_4_1","first-page":"1563","article-title":"Long\u2010Term Survivorship of Total Hip Arthroplasty With Highly Cross\u2010Linked Polyethylene for Osteonecrosis","volume":"101","author":"Hart A.","year":"2019","journal-title":"Journal of Bone and Joint Surgery. 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