Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S

Fic, Anja; Mlakar, Simona Jurković; Juvan, Peter; Mlakar, Vid; Marc, Janja; Dolenc, Marija Sollner; Broberg, Karin; Mašič, Lucíja Peterlin

doi:10.1016/j.tiv.2015.03.014

Cited by 49 publications

(31 citation statements)

References 61 publications

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“…After three months of exposure, BPAF and BPS significantly enriched 5 and 11 skeletal biological processes according to the genome-wide gene expression assay, but BPA exposure was not associated with changes in any skeletal genes 29 . Some of the processes enhanced by BPAF and BPS included development of embryonic skeletal system, osteoclast differentiation and hedgehog signalling pathway 29 . Bisphenol AF by itself enriched TGF-beta signalling pathway whereas BPS reduced expression of genes related to Wnt signalling pathway (low-density lipoprotein receptor-related protein 5 and Wnt5A) and specific osteoblast markers (RUNX-2, osteoprotegerin, collagen type 1 alpha 1) 29 .…”

Section: Evidence From In Vitro Studiesmentioning

confidence: 90%

“…The effects of long-term exposure to BPA and its analogues, bisphenol AF (BPAF) and bisphenol S (BPS) (10 nM) on human osteosarcoma cells were compared 29 . After three months of exposure, BPAF and BPS significantly enriched 5 and 11 skeletal biological processes according to the genome-wide gene expression assay, but BPA exposure was not associated with changes in any skeletal genes 29 . Some of the processes enhanced by BPAF and BPS included development of embryonic skeletal system, osteoclast differentiation and hedgehog signalling pathway 29 .…”

Section: Evidence From In Vitro Studiesmentioning

confidence: 99%

“…Some of the processes enhanced by BPAF and BPS included development of embryonic skeletal system, osteoclast differentiation and hedgehog signalling pathway 29 . Bisphenol AF by itself enriched TGF-beta signalling pathway whereas BPS reduced expression of genes related to Wnt signalling pathway (low-density lipoprotein receptor-related protein 5 and Wnt5A) and specific osteoblast markers (RUNX-2, osteoprotegerin, collagen type 1 alpha 1) 29 . The differential effects of BPA analogues on skeletal process might be related to their affinity towards cell receptors.…”

Section: Evidence From In Vitro Studiesmentioning

confidence: 99%

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A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

2018

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Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.

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Section: Evidence From In Vitro Studiesmentioning

confidence: 90%

Section: Evidence From In Vitro Studiesmentioning

confidence: 99%

Section: Evidence From In Vitro Studiesmentioning

confidence: 99%

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A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

2018

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“…However, BPS also seems to have a low-dose effect similar to BPA and has been found to adversely affect neurogenesis of zebrafish and Wistar rats [ 120 , 121 ]. BPS can also alter gene transcription in a human osteosarcoma cell line related to immunity (e.g., downregulating CCL2) [ 122 ]. However, research on developmental BPS exposure’s effects on the immune system is needed to draw a conclusion.…”

Section: Bisphenol S: An Alternative For Bpamentioning

confidence: 99%

Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

Huang

Guo

2016

Toxics

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Bisphenol A (BPA), used in polycarbonate plastics and epoxy resins, has a widespread exposure to humans. BPA is of concern for developmental exposure resulting in immunomodulation and disease development due to its ability to cross the placental barrier and presence in breast milk. BPA can use various mechanisms to modulate the immune system and affect diseases, including agonistic and antagonistic effects on many receptors (e.g., estrogen receptors), epigenetic modifications, acting on cell signaling pathways and, likely, the gut microbiome. Immune cell populations and function from the innate and adaptive immune system are altered by developmental BPA exposure, including decreased T regulatory (Treg) cells and upregulated pro-and anti-inflammatory cytokines and chemokines. Developmental BPA exposure can also contribute to the development of type 2 diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated by BPA, although more research is needed. Additionally, BPA analogs, such as bisphenol S (BPS), have been increasing in use, and currently, little is known about their immune effects. Therefore, more studies should be conducted to determine if developmental exposure BPA and its analogs modulate immune responses and lead to immune-related diseases.

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“…33 Genomewide gene expression studies found that PDSS1 expression levels were upregulated by exposing human osteosarcoma cells to bisphenol A analogs. 34 A pilot study also suggested that significant upregulation of PDSS1 expression levels in the whole blood were associated with susceptibility to type 2 diabetes and therapeutic response. 35 Genetic variants in PDSS1 have also been identified in patients with mitochondrial disorders, suggesting its potential role in mitochondrial function.…”

mentioning

confidence: 99%

Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma‐specific survival

Dai

Liu

Chen

et al. 2020

Molecular Carcinogenesis

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A few single-nucleotide polymorphisms (SNPs) have been identified to be associated with cutaneous melanoma (CM) survival through genome-wide association studies, but stringent multiple testing corrections required for the hypothesis-free testing may have masked some true associations. Using a hypothesis-driven analysis approach, we sought to evaluate associations between SNPs in ketone body metabolic pathway genes and CM survival. We comprehensively assessed associations between 4196 (538 genotyped and 3658 imputed) common SNPs in 44 ketone body metabolic pathway genes and CM survival, using a dataset of 858 patients of a casecontrol study from The University of Texas M.D. Anderson Cancer Center as the discovery set and another dataset of 409 patients from the Nurses' Health Study and the Health Professionals Follow-up Study as the replication set. There were 95/858 (11.1%) and 48/409 (11.7%) patients who died of CM, respectively. We identified two independent SNPs (ie, PDSS1 rs12254548 G>C and SLC16A6 rs71387392 G>A) that were associated with CM survival, with allelic hazards ratios of 0.58 (95% confidence interval [CI] = 0.44-0.76, P = 9.00 × 10 −5 ) and 1.98 (95% CI = 1.34-2.94, P = 6.30 × 10 −4 ), respectively. Additionally, associations between genotypes of the SNPs and messenger RNA expression levels of their Abbreviations: CI, confidence interval; CM, cutaneous melanoma; CMSS, cutaneous melanoma-specific survival; GWAS, genome-wide association study; HPFS, The Health Professionals Follow-up Study; HR adj , adjusted hazards ratio; LD, linkage disequilibrium; MDACC, The University of Texas MD Anderson Cancer Center; NHS, The Nurses' Health Study; PDSS1, decaprenyl diphosphate synthase subunit 1; SLC16A6, solute carrier family 16 member 6; SNP, single-nucleotide polymorphism. d BFDP was used for multiple test correction with detected a highest hazard ratio of 2.0 and a prior probability of 0.1. e Adjusted for age and sex in an additive genetic model. f Meta-analysis in a fix-effects model. Abbreviations: BFDP, Bayesian false-discovery probability; CI, confidence interval; EAF, effect allele frequency; GWAS, genome-wide association study; HPFS, Health Professionals Follow-up Study; HR, hazards ratio; MDACC, The University of Texas MD Anderson Cancer Center; NHS, Nurses' Health Study; P het , P value for heterogeneity by Cochrane's Q test; PDSS1, decaprenyl diphosphate synthase subunit 1; SLC16A6, solute carrier family 16 member 6; SNP, single-nucleotide polymorphism. 644 | DAI ET AL.

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Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S

Cited by 49 publications

References 61 publications

A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

A Review on the Effects of Bisphenol A and Its Derivatives on Skeletal Health

Developmental Bisphenol A Exposure Modulates Immune-Related Diseases

Genetic variants in PDSS1 and SLC16A6 of the ketone body metabolic pathway predict cutaneous melanoma‐specific survival

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