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 activi...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324016002 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823856951863279616 |
|---|---|
| author | Liming Xue Jiale Xu Ping Xiao Yiping Jiang Yuanjie Lin Chao Feng Yu’e Jin Zhijun Zhou Guoquan Wang Dasheng Lu |
| author_facet | Liming Xue Jiale Xu Ping Xiao Yiping Jiang Yuanjie Lin Chao Feng Yu’e Jin Zhijun Zhou Guoquan Wang Dasheng Lu |
| author_sort | Liming Xue |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fd52265edcbc4e6684c25e0d3c31e6ff |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-fd52265edcbc4e6684c25e0d3c31e6ff2025-02-12T05:29:28ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01290117524Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblastLiming Xue0Jiale Xu1Ping Xiao2Yiping Jiang3Yuanjie Lin4Chao Feng5Yu’e Jin6Zhijun Zhou7Guoquan Wang8Dasheng Lu9Division of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, ChinaDivision of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, ChinaDivision of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, ChinaSchool of Pharmacy, Naval Medical University, Shanghai 200433, ChinaDivision of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, ChinaDivision of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, ChinaDivision of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, ChinaSchool of Public Health, Fudan University, Shanghai 200032, ChinaDivision of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; Correspondence to: Institution of Chemical and Toxicity Assessment, Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhongshan Road, Shanghai 200336, China.Division of Chemical Toxicity and Safety Assessment, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China; Correspondence to: Institution of Chemical and Toxicity Assessment, Shanghai Municipal Center for Disease Control and Prevention, 1380 Zhongshan Road, Shanghai 200336, China.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.http://www.sciencedirect.com/science/article/pii/S0147651324016002Perfluorooctane sulfonate (PFOS)TranscriptomicsFoxO1Osteoblastic bone formationOxidative Stress |
| spellingShingle | Liming Xue Jiale Xu Ping Xiao Yiping Jiang Yuanjie Lin Chao Feng Yu’e Jin Zhijun Zhou Guoquan Wang Dasheng Lu Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast Ecotoxicology and Environmental Safety Perfluorooctane sulfonate (PFOS) Transcriptomics FoxO1 Osteoblastic bone formation Oxidative Stress |
| title | Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast |
| title_full | Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast |
| title_fullStr | Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast |
| title_full_unstemmed | Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast |
| title_short | Perfluorooctane sulfonate (PFOS) induced bone loss by inhibiting FoxO1-mediated defense against oxidative stress in osteoblast |
| title_sort | perfluorooctane sulfonate pfos induced bone loss by inhibiting foxo1 mediated defense against oxidative stress in osteoblast |
| topic | Perfluorooctane sulfonate (PFOS) Transcriptomics FoxO1 Osteoblastic bone formation Oxidative Stress |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324016002 |
| work_keys_str_mv | AT limingxue perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT jialexu perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT pingxiao perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT yipingjiang perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT yuanjielin perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT chaofeng perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT yuejin perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT zhijunzhou perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT guoquanwang perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast AT dashenglu perfluorooctanesulfonatepfosinducedbonelossbyinhibitingfoxo1mediateddefenseagainstoxidativestressinosteoblast |