Possible ways the chemical DEHP may cause bone loss, shown by combining network analysis and lab tests

Exposure to di-2-ethylhexyl phthalate (DEHP) is associated with impaired osteogenic differentiation and altered expression of key targets in osteoporosis.

• Thirty-two potential targets related to DEHP and osteoporosis were identified.
• DEHP may affect osteoporosis primarily through estrogen and MAPK/PI3K-Akt signaling pathways, as well as cellular senescence.
• Key targets TNF, AKT1, MAPK3, and CYP17A1 were prioritized based on computational screening and molecular docking.
• DEHP exposure resulted in upregulation of TNF and downregulation of AKT1, MAPK3, and CYP17A1.
• Impaired osteogenic differentiation of MC3T3-E1 cells was observed, indicated by decreased ALP activity and mineralization capacity.
• Downregulation of important osteogenic markers, including Runx2, ALP, OPN, and OCN, was noted with DEHP exposure.

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