Effectes of perfluorooctanoic acid exposure on mouse embryonic osteoblast precursor cells and its molecular mechanisms
10.19428/j.cnki.sjpm.2025.24804
- VernacularTitle:全氟辛酸暴露小鼠胚胎成骨细胞前体细胞作用及其分子机制研究
- Author:
Liming XUE
1
;
Jiale XU
1
;
Yuanjie LIN
1
;
Yu'e JIN
1
;
Dasheng LU
1
;
Guoquan WANG
1
Author Information
1. Division of Chemical Toxicity and Safety Assessment, Shanghai Municiple Center for Disease Control and Prevention, Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Ministry of Ecology and Environment, Shanghai 201107, China
- Publication Type:Journal Article
- Keywords:
perfluorooctanoic acid;
bone loss;
transcriptomics;
energy metabolism;
β-oxidation of fatty acid
- From:
Shanghai Journal of Preventive Medicine
2025;37(7):629-635
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the biological mechanism of bone loss caused by perfluorooctanoic acid (PFOA) through transcriptomic analysis, and to provide new insights into regulating perfluoroalkyl substances (PFAS) applications and the prevention of hazards affecting bone health. MethodsMouse embryonic osteoblast precursor cells (MC3T3-E1) were exposed to 0.1, 1, 10, and 100 μmol·L-¹ PFOA for 24 hours to assess the effects on cell viability and alkaline phosphatase (ALP) activity, and to determine the critical concentration of PFOA toxicity. The transcriptome sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) induced by PFOA. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted to identify significantly affected gene pathways. Additionally, Seahorse XF metabolic phenotyping and reverse transcription polymerase chain reaction (RT-PCR) were used to validate the key pathways. ResultsExposure to 10 and 100 μmol·L-¹ PFOA significantly reduced the cell viability and ALP activity of MC3T3-E1 cells. Therefore, the results of transcriptomic analysis for 10 μmol‧L-1 PFOA exposure found that a total of 80 DEGs were identified, including 32 upregulated genes and 48 downregulated genes. According to GO analysis, PFOA mainly affected cellular components such as mitochondrion and nucleus, molecular functions involving GTPase activity and GTP binding, as well as biological process related to mRNA processing. GSEA identified the downregulation of the β-oxidation of fatty acid pathway in mitochondria. Metabolic phenotyping reserches showed that PFOA indeed reduced mitochondrial aerobic respiration capacity and adenosine triphosphate (ATP) production, and the ratio of ATP production from cellular aerobic respiration to glycolysis was significantly decreased as well. The mRNA expression of glucose metabolism-related genes (GK, G6PD, and CS), as well as fatty acid metabolism-related genes (CPT1A and CPT2), were significantly downregulated. ConclusionPFOA reduces bone formation by inhibiting energy metabolism and β-oxidation of fatty acid pathways in osteoblasts, whihc lays the foundation for revealing the mechanism of PFOA exposure induced bone loss.
