Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation
As the primary molecular target, there is still a gap between the peroxisome proliferator-activated receptors (PPARs) regulation and the adverse health effects caused by per- and polyfluoroalkyl substances (PFASs). The effects of PFASs on cellular differentiation regulated by PPARs is likely signifi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412022005116 |
| _version_ | 1811206827142021120 |
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| author | Hui Qin Yuxin Niu Haiyang Luan Minghan Li Lu Zheng Yifan Pan Wei Liu |
| author_facet | Hui Qin Yuxin Niu Haiyang Luan Minghan Li Lu Zheng Yifan Pan Wei Liu |
| author_sort | Hui Qin |
| collection | DOAJ |
| description | As the primary molecular target, there is still a gap between the peroxisome proliferator-activated receptors (PPARs) regulation and the adverse health effects caused by per- and polyfluoroalkyl substances (PFASs). The effects of PFASs on cellular differentiation regulated by PPARs is likely significant given the association of PFASs exposure with obesity and decreased bone density. Human mesenchymal stem cells (hMSCs) were used as an in vitro model to assess the roles of PPAR subtypes in the multipotent differentiation of hMSCs affected by perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their replacement compounds. PFASs increased the expression of three PPAR subtypes in proliferating and differentiating hMSCs. Meanwhile, PFOS and PFOA decreased osteogenesis, enhanced adipogenesis, and increased bone turnover in hMSCs. Similarly, PFOA alternatives, hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA), exhibited similar or even higher potency in affecting stem cell differentiation compared with PFOA. Perfluorohexanesulfonate (PFHxS) inhibited osteogenesis with comparable potency to PFOS. In contrast, 6:2 chlorinated poly-fluoroalkyl ether sulfonate (6:2Cl-PFESA) enhanced osteogenesis. PPARβ expression is significantly positively correlated with osteogenesis and osteoprotegerin (OPG) secretion in 6:2Cl-PFESA treated cells. shRNA knockdown of PPARβ remarkably reversed the osteogenic effects of 6:2Cl-PFESA and enhanced the adipogenic effects of the six chemicals. The results suggested that the adverse effects and relative potency of PFASs on the multipotent differentiation of hMSCs were dependent on the integrated action of the three PPAR subtypes, which facilitates a better understanding of the molecular initiating events of PFASs. The present study may well explain the mechanism of the decreased bone density and increased obesity incidence among those exposed to legacy PFASs, and indicates the necessity of further health risk assessment for the alternatives. |
| first_indexed | 2024-04-12T03:54:35Z |
| format | Article |
| id | doaj.art-f688674fc5474884ae22b2dfabb58efb |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-12T03:54:35Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-f688674fc5474884ae22b2dfabb58efb2022-12-22T03:48:53ZengElsevierEnvironment International0160-41202022-12-01170107584Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiationHui Qin0Yuxin Niu1Haiyang Luan2Minghan Li3Lu Zheng4Yifan Pan5Wei Liu6Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, ChinaKey Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, ChinaKey Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, ChinaKey Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, ChinaKey Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, ChinaCollege of Life Sciences, Hebei University, Baoding 071002, ChinaKey Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), School of Environmental Science and Technology, Dalian University of Technology, Dalian 116024, China; Corresponding author.As the primary molecular target, there is still a gap between the peroxisome proliferator-activated receptors (PPARs) regulation and the adverse health effects caused by per- and polyfluoroalkyl substances (PFASs). The effects of PFASs on cellular differentiation regulated by PPARs is likely significant given the association of PFASs exposure with obesity and decreased bone density. Human mesenchymal stem cells (hMSCs) were used as an in vitro model to assess the roles of PPAR subtypes in the multipotent differentiation of hMSCs affected by perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their replacement compounds. PFASs increased the expression of three PPAR subtypes in proliferating and differentiating hMSCs. Meanwhile, PFOS and PFOA decreased osteogenesis, enhanced adipogenesis, and increased bone turnover in hMSCs. Similarly, PFOA alternatives, hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA), exhibited similar or even higher potency in affecting stem cell differentiation compared with PFOA. Perfluorohexanesulfonate (PFHxS) inhibited osteogenesis with comparable potency to PFOS. In contrast, 6:2 chlorinated poly-fluoroalkyl ether sulfonate (6:2Cl-PFESA) enhanced osteogenesis. PPARβ expression is significantly positively correlated with osteogenesis and osteoprotegerin (OPG) secretion in 6:2Cl-PFESA treated cells. shRNA knockdown of PPARβ remarkably reversed the osteogenic effects of 6:2Cl-PFESA and enhanced the adipogenic effects of the six chemicals. The results suggested that the adverse effects and relative potency of PFASs on the multipotent differentiation of hMSCs were dependent on the integrated action of the three PPAR subtypes, which facilitates a better understanding of the molecular initiating events of PFASs. The present study may well explain the mechanism of the decreased bone density and increased obesity incidence among those exposed to legacy PFASs, and indicates the necessity of further health risk assessment for the alternatives.http://www.sciencedirect.com/science/article/pii/S0160412022005116Perfluorinated substancesPPARsHuman mesenchymal stem cellsMultipotent differentiationMolecular initiating event |
| spellingShingle | Hui Qin Yuxin Niu Haiyang Luan Minghan Li Lu Zheng Yifan Pan Wei Liu Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation Environment International Perfluorinated substances PPARs Human mesenchymal stem cells Multipotent differentiation Molecular initiating event |
| title | Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation |
| title_full | Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation |
| title_fullStr | Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation |
| title_full_unstemmed | Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation |
| title_short | Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation |
| title_sort | effects of legacy and emerging per and polyfluoroalkyl substances on pparα β γ regulation and osteogenic adipogenic differentiation |
| topic | Perfluorinated substances PPARs Human mesenchymal stem cells Multipotent differentiation Molecular initiating event |
| url | http://www.sciencedirect.com/science/article/pii/S0160412022005116 |
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