Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation

The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the corre...

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Main Authors: Yaoyao Nie, Houpu Liu, Runtao Wu, Jiayao Fan, Ye Yang, Wenxia Zhao, Jiapeng Bao, Zhenqiang You, Fan He, Yingjun Li
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651324002938
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author Yaoyao Nie
Houpu Liu
Runtao Wu
Jiayao Fan
Ye Yang
Wenxia Zhao
Jiapeng Bao
Zhenqiang You
Fan He
Yingjun Li
author_facet Yaoyao Nie
Houpu Liu
Runtao Wu
Jiayao Fan
Ye Yang
Wenxia Zhao
Jiapeng Bao
Zhenqiang You
Fan He
Yingjun Li
author_sort Yaoyao Nie
collection DOAJ
description The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.
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spelling doaj.art-b683b0a01f794e3ea1d28f029f9bab202024-03-27T04:51:24ZengElsevierEcotoxicology and Environmental Safety0147-65132024-04-01274116217Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentationYaoyao Nie0Houpu Liu1Runtao Wu2Jiayao Fan3Ye Yang4Wenxia Zhao5Jiapeng Bao6Zhenqiang You7Fan He8Yingjun Li9Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, ChinaSchool of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, ChinaDepartment of Orthopaedics, the Second Affiliated Hospital of Zhejiang University, Hangzhou 310058, ChinaDepartment of Food Science and Engineering, School of Public Health, Hangzhou Medical College, Hangzhou 310053, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang 310051, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, China; Correspondence to: Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, 481 Binwen Road, Hangzhou 310053, China.The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.http://www.sciencedirect.com/science/article/pii/S0147651324002938OsteoarthritisBenzophenone-3SPARCFerroptosis
spellingShingle Yaoyao Nie
Houpu Liu
Runtao Wu
Jiayao Fan
Ye Yang
Wenxia Zhao
Jiapeng Bao
Zhenqiang You
Fan He
Yingjun Li
Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation
Ecotoxicology and Environmental Safety
Osteoarthritis
Benzophenone-3
SPARC
Ferroptosis
title Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation
title_full Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation
title_fullStr Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation
title_full_unstemmed Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation
title_short Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics analyses and biological experimentation
title_sort interference with sparc inhibits benzophenone 3 induced ferroptosis in osteoarthritis evidence from bioinformatics analyses and biological experimentation
topic Osteoarthritis
Benzophenone-3
SPARC
Ferroptosis
url http://www.sciencedirect.com/science/article/pii/S0147651324002938
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