{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:21:02Z","timestamp":1789600862772,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Artificial joint replacement surgery is often accompanied by osteolysis induced aseptic loosening around the prosthesis. Wear particles from joint replacement are thought to be one of the main factors leading to local inflammation and osteolysis at the prosthesis site. The aim of this study was to investigate the molecular mechanism of osteoclast formation and dissolution induced by wear particles and the potential roles of Netrin\u20101, the ERK1\/2 pathway and autophagy activation in this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The messenger RNA levels in cells and tissues were detected with real\u2010time quantitative PCR. The western blotting was used to detect the expression of proteins. A CCK\u20108 kit was used to detect the viability of RAW 264.7 cells. Moreover, an air pouch model of bone resorption was established. Immunohistochemistry was used to detect the expression of TRAP and Netrin\u20101 in rat bone tissue. Cell culture supernatants were collected in the rat air pouch model of bone resorption, and the levels of RANKL and OPG were detected with enzyme\u2010linked immunosorbent assay. The protein levels of TRAP and Netrin\u20101 in bone tissue were examined by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Titanium wear particles induced osteoclast formation and autophagy activation. Moreover, blocking autophagy suppressed the osteoclastogenesis after exposure to wear particles in vitro. The activation of the ERK1\/2 pathway and the overexpression of Netrin\u20101 were both found to play important roles in osteoclastogenesis mediated by autophagy. Moreover, 3\u2010MA effectively decreased the secretion of proinflammatory cytokines mediated by wear particles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Blockade of autophagy inhibits the osteoclastogenesis and inflammation induced by wear particles, thus potentially providing novel treatment strategies for abnormal osteoclastogenesis and aseptic prosthesis loosening induced by wear particles.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbin.11544","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T12:33:24Z","timestamp":1609590804000},"page":"612-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Netrin\u20101 regulates ERK1\/2 signaling pathway and autophagy activation in wear particle\u2010induced osteoclastogenesis"],"prefix":"10.1002","volume":"45","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"},{"name":"Department of Orthopedics Affiliated Hospital of Yan'an University  Yan'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibiao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Hospital of Yan'an University  Yan'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Hospital of Yan'an University  Yan'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Hospital of Yan'an University  Yan'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Affiliated Hospital of Yan'an University  Yan'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42288"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2014.06.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.H.00155"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13758-012-0034-x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210500109"},{"key":"e_1_2_8_7_1","first-page":"183","article-title":"A simplified method for the generation of human osteoclasts in vitro","volume":"2","author":"Cody J. 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