Effects of legacy and emerging per- and polyfluoroalkyl substances on PPARα/β/γ regulation and osteogenic/adipogenic differentiation

Reciprocal Effect of Environmental Stimuli to Regulate the Adipogenesis and Osteogenesis Fate Decision in Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs)

“…HFPO-DA, on the other hand, was the most potent agonist for Pparβ, followed by HFPO-TA and PFHxS. HFPO-DA also demonstrated a strong potency in Pparγ activation, followed by PFOS and HFPO-TA [46].…”

“…In hBM-MSCs, during proliferation, PFOA, PFOS, and PFHxS upregulated Pparα expression levels, while 6:2Cl-PFESA showed the strongest induction of Pparβ expression. All tested PFASs upregulated the Pparγ mRNA expression, with HFPO-DA and PFHxS among the most potent Pparγ activators, during cell proliferation [46]. During differentiation, 6:2Cl-PFESA was not an activator of Pparγ but rather the most potent activator of Pparα, followed by PFOS and PFOA.…”

“…Human exposure to PFASs is ubiquitous in water, food, and air [45]. Qin et al, evaluated the adipogenesis and osteogenesis of perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and their replacement compounds [6:2 chlorinated polyfluorinated ether sulfonate (6:2Cl-PFESA), as well as hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA)], in human BM-MSCs [46]. There are three subtypes of PPARs that modulate biological function [46][47][48].…”

“…Qin et al, evaluated the adipogenesis and osteogenesis of perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and their replacement compounds [6:2 chlorinated polyfluorinated ether sulfonate (6:2Cl-PFESA), as well as hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA)], in human BM-MSCs [46]. There are three subtypes of PPARs that modulate biological function [46][47][48]. Pparα activation increases BMD; Pparγ activation promotes adipogenic differentiation [49,50], whereas Pparβ activation promotes osteogenic differentiation via Wnt/β-catenin signaling [48].…”

“…Pparα activation increases BMD; Pparγ activation promotes adipogenic differentiation [49,50], whereas Pparβ activation promotes osteogenic differentiation via Wnt/β-catenin signaling [48]. The effects of PFASs (up to 10 µM) on PPARs expression are dependent on cellular status: proliferating or differentiating [46]. In hBM-MSCs, during proliferation, PFOA, PFOS, and PFHxS upregulated Pparα expression levels, while 6:2Cl-PFESA showed the strongest induction of Pparβ expression.…”