Osthole ameliorates wear particle-induced osteogenic impairment by mitigating endoplasmic reticulum stress via PERK signaling cascade

作者：Xin Yu, Juan Jiang, Li Cheng, Yang Wang, Zhengrong Ren, Jianlun Hu, Tao Yuan, Yongjie Wu, Dongsheng Wang, Ziying Sun, Qi Wu, Bin Chen, Fang Peng, Hao Ding, Jia Meng, Hui Jiang, Jianning Zhao, Nirong Bao · 发表于：Molecular Medicine · 年份：2024 · DOI：10.1186/s10020-024-01034-z · 被引用次数：5 · 研究领域：Orthopaedic implants and arthroplasty、Bone Metabolism and Diseases、Spondyloarthritis Studies and Treatments

BACKGROUND: Periprosthetic osteolysis and subsequent aseptic loosening are the leading causes of failure following total joint arthroplasty. 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. METHODS: 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. RESULTS: particles (TiPs)-induced osteolysis by enhancing osteogenesis in a mouse calvarial model. Furthermore...