{"title":"全氟辛烷磺酸(PFOS)通过抑制 FoxO1 介导的成骨细胞对氧化应激的防御,诱导骨质流失。","authors":"Liming Xue, Jiale Xu, Ping Xiao, Yiping Jiang, Yuanjie Lin, Chao Feng, Yu'e Jin, Zhijun Zhou, Guoquan Wang, Dasheng Lu","doi":"10.1016/j.ecoenv.2024.117524","DOIUrl":null,"url":null,"abstract":"<p><p>Exposure to perfluorooctane sulfonate (PFOS) has been associated with lower bone density and the occurrence of osteoporosis in human studies, but the effects and mechanisms of PFOS induces bone loss is not well understood. Our research is aimed at examining the effects of PFOS on osteoblastic activity and investigating the toxicological mechanisms of PFOS-induced bone loss. Cell proliferation, ALP activity, bone nodule formation, ROS levels, and cell apoptosis were assessed after treating osteoblasts with different concentrations of PFOS. Through transcriptome analysis, the differentially expressed genes (DEGs) were screened and the biofunctions were elucidated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and The Gene Set Enrichment Analysis (GSEA). Vation of important genes and protein expression was accomplished using RT-PCR and Western blot methods, respectively. The results show that PFOS can reduce bone formation markers and improve oxidative stress and cell apoptosis. The DEGs in PFOS-treated groups were involved in multiple pathways, including FoxO, HIF-1, Rap1, Hippo, and sphingolipid signaling. FoxO1 was validated as the key gene which regulates osteogenic differentiation and redox status. Our findings suggest that PFOS reduces bone formation through FoxO1-mediated oxidative stress and apoptosis, as well as inhibition of the OPG/RANKL and FoxO1/β-catenin pathways. It will be beneficial for early intervention or treatment of PFOS-induced bone loss, highlighting the importance of regulatory measures to limit human exposure to PFOS.</p>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":"290 ","pages":"117524"},"PeriodicalIF":6.2000,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast.\",\"authors\":\"Liming Xue, Jiale Xu, Ping Xiao, Yiping Jiang, Yuanjie Lin, Chao Feng, Yu'e Jin, Zhijun Zhou, Guoquan Wang, Dasheng Lu\",\"doi\":\"10.1016/j.ecoenv.2024.117524\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Exposure to perfluorooctane sulfonate (PFOS) has been associated with lower bone density and the occurrence of osteoporosis in human studies, but the effects and mechanisms of PFOS induces bone loss is not well understood. Our research is aimed at examining the effects of PFOS on osteoblastic activity and investigating the toxicological mechanisms of PFOS-induced bone loss. Cell proliferation, ALP activity, bone nodule formation, ROS levels, and cell apoptosis were assessed after treating osteoblasts with different concentrations of PFOS. Through transcriptome analysis, the differentially expressed genes (DEGs) were screened and the biofunctions were elucidated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and The Gene Set Enrichment Analysis (GSEA). Vation of important genes and protein expression was accomplished using RT-PCR and Western blot methods, respectively. The results show that PFOS can reduce bone formation markers and improve oxidative stress and cell apoptosis. The DEGs in PFOS-treated groups were involved in multiple pathways, including FoxO, HIF-1, Rap1, Hippo, and sphingolipid signaling. FoxO1 was validated as the key gene which regulates osteogenic differentiation and redox status. Our findings suggest that PFOS reduces bone formation through FoxO1-mediated oxidative stress and apoptosis, as well as inhibition of the OPG/RANKL and FoxO1/β-catenin pathways. It will be beneficial for early intervention or treatment of PFOS-induced bone loss, highlighting the importance of regulatory measures to limit human exposure to PFOS.</p>\",\"PeriodicalId\":303,\"journal\":{\"name\":\"Ecotoxicology and Environmental Safety\",\"volume\":\"290 \",\"pages\":\"117524\"},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2024-12-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ecotoxicology and Environmental Safety\",\"FirstCategoryId\":\"93\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ecoenv.2024.117524\",\"RegionNum\":2,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENVIRONMENTAL SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1016/j.ecoenv.2024.117524","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast.
Exposure to perfluorooctane sulfonate (PFOS) has been associated with lower bone density and the occurrence of osteoporosis in human studies, but the effects and mechanisms of PFOS induces bone loss is not well understood. Our research is aimed at examining the effects of PFOS on osteoblastic activity and investigating the toxicological mechanisms of PFOS-induced bone loss. Cell proliferation, ALP activity, bone nodule formation, ROS levels, and cell apoptosis were assessed after treating osteoblasts with different concentrations of PFOS. Through transcriptome analysis, the differentially expressed genes (DEGs) were screened and the biofunctions were elucidated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and The Gene Set Enrichment Analysis (GSEA). Vation of important genes and protein expression was accomplished using RT-PCR and Western blot methods, respectively. The results show that PFOS can reduce bone formation markers and improve oxidative stress and cell apoptosis. The DEGs in PFOS-treated groups were involved in multiple pathways, including FoxO, HIF-1, Rap1, Hippo, and sphingolipid signaling. FoxO1 was validated as the key gene which regulates osteogenic differentiation and redox status. Our findings suggest that PFOS reduces bone formation through FoxO1-mediated oxidative stress and apoptosis, as well as inhibition of the OPG/RANKL and FoxO1/β-catenin pathways. It will be beneficial for early intervention or treatment of PFOS-induced bone loss, highlighting the importance of regulatory measures to limit human exposure to PFOS.
期刊介绍:
Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.