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Osteogenic impairment induced by wear particles is regarded as a crucial contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress identified as a key underlying mechanism. Therefore, identifying potential therapeutic targets and agents that can regulate ER stress adaption in osteoblasts is necessary for arresting aseptic loosening. Osthole (OST), a natural coumarin derivative, has demonstrated promising osteogenic properties and the ability to modulate ER stress adaption in various diseases. However, the impact of OST on ER stress-mediated osteogenic impairment caused by wear particles remains unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>TiAl<jats:sub>6<\/jats:sub>V<jats:sub>4<\/jats:sub> particles (TiPs) were sourced from the prosthesis of patients who underwent revision hip arthroplasty due to aseptic loosening. A mouse calvarial osteolysis model was utilized to explore the effects of OST on TiPs-induced osteogenic impairment in vivo. Primary mouse osteoblasts were employed to investigate the impact of OST on ER stress-mediated osteoblast apoptosis and osteogenic inhibition induced by TiPs in vitro. The mechanisms underlying OST-modulated alleviation of ER stress induced by TiPs were elucidated through Molecular docking, immunochemistry, PCR, and Western blot analysis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, we found that OST treatment effectively mitigated TiAl<jats:sub>6<\/jats:sub>V<jats:sub>4<\/jats:sub> particles (TiPs)-induced osteolysis by enhancing osteogenesis in a mouse calvarial model. Furthermore, we observed that OST could attenuate ER stress-mediated apoptosis and osteogenic reduction in osteoblasts exposed to TiPs in vitro and in vivo. Mechanistically, we demonstrated that OST exerts bone-sparing effects on stressed osteoblasts upon TiPs exposure by specifically suppressing the ER stress-dependent PERK signaling cascade.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Osthole ameliorates wear particle-induced osteogenic impairment by mitigating endoplasmic reticulum stress via PERK signaling cascade. These findings suggest that OST may serve as a potential therapeutic agent for combating wear particle-induced osteogenic impairment, offering a novel alternative strategy for managing aseptic prosthesis loosening.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10020-024-01034-z","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T10:58:03Z","timestamp":1734692283000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Osthole ameliorates wear particle-induced osteogenic impairment by mitigating endoplasmic reticulum stress via PERK signaling cascade"],"prefix":"10.1186","volume":"30","author":[{"given":"Xin","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengrong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianning","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirong","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"1034_CR48","doi-asserted-by":"publisher","first-page":"110935","DOI":"10.1016\/j.cellsig.2023.110935","volume":"113","author":"Y An","year":"2024","unstructured":"An Y, Xu C, Liu W, Jiang J, Ye P, Yang M, Zhu W, Yu J, Yu M, Sun W, Hong J, Qiu H, Wei W, Zhang S. 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