{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T06:32:19Z","timestamp":1778394739915,"version":"3.51.4"},"reference-count":94,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T00:00:00Z","timestamp":1490572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK2012776"],"award-info":[{"award-number":["BK2012776"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>Macrophage apoptosis in interface membrane, which occurs through either death receptor, mitochondrion, or endoplasmic reticulum (<jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>) stress pathways, has been suggested to play an important role in promoting osteolysis. However, how and why macrophage apoptosis originates and the correlation among these apoptotic pathways is not yet clear. The objective of this study was to identify the apoptotic mechanism of macrophages, and to explore the relationship between the apoptotic pathways and progression of osteolysis. Transmission electron microscopy (<jats:styled-content style=\"fixed-case\">TEM<\/jats:styled-content>) was utilized to analyze the tissue ultrastructure of wear particles, and <jats:italic>in situ<\/jats:italic> apoptotic macrophage identification was performed by <jats:styled-content style=\"fixed-case\">TUNEL<\/jats:styled-content> staining. We analyzed the expression of the key biomarkers of apoptotic pathways via immunohistochemistry and Western blotting. Our results demonstrated that the majority of wear particles within osteolytic interface membrane was in the 30\u201360 nm range, and that macrophage apoptotic ratio increased along with osteolysis progression. Normal hip dysplasia and mechanical loosening of tissues showed low expression levels of biomarkers for <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress (Ca<jats:sup>2+<\/jats:sup>, <jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>, cleaved Caspase\u20104, <jats:styled-content style=\"fixed-case\">IRE<\/jats:styled-content>1\u2010\u03b1, Grp78\/Bip, and <jats:styled-content style=\"fixed-case\">CHOP<\/jats:styled-content>), mitochondrion (Bcl\u20102, Bax, and Cytochrome c), and death receptor (Fas and cleaved Caspase\u20108) pathways, while osteolytic interface membrane tissues expressed high levels of these biomarkers. In addition, we found that the <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content> stress intensity was in complete conformity with mitochondrial dysfunction and was consistent with the results of death receptor activation. Thus, our findings suggested that wear particles generated at implant interface can accelerate macrophage apoptosis through changes in apoptotic pathways and ultimately aggravate the symptom of osteolysis. These data represent a preferential apoptotic signaling pathway of macrophages as specific target points for the prevention and therapeutic modulation of periprosthetic osteolysis.<\/jats:p>","DOI":"10.1111\/apm.12679","type":"journal-article","created":{"date-parts":[[2017,3,27]],"date-time":"2017-03-27T10:25:45Z","timestamp":1490610345000},"page":"565-578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Apoptotic pathways of macrophages within osteolytic interface membrane in periprosthestic osteolysis after total hip replacement"],"prefix":"10.1111","volume":"125","author":[{"given":"Guoyin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Jinling Hospital affiliated to School of Medicine Nanjing University and State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Nanjing China"},{"name":"Department of Orthopaedics Bayi Hospital 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