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Elucidating the mechanism of triphenyl phosphate interference in bone metabolism via network toxicology and molecular

Min Xu1, Yinxiang Wu2, Jiaqi Meng2

  • 1Department of Trauma Orthopedic, First Affiliated Hospital of Naval Medical University, Shanghai, China.

Frontiers in Endocrinology
|July 22, 2025
PubMed
Abstract

Insights

Triphenyl phosphate (TPhP) disrupts bone metabolism by affecting key proteins and signaling pathways, posing potential health risks. Further research is needed to understand its impact on bone homeostasis.

Area of Science:

  • Environmental toxicology
  • Molecular biology
  • Biochemistry

Background:

  • Organophosphate flame retardants like triphenyl phosphate (TPhP) are widely used.
  • Environmental chemicals can impact bone homeostasis.
  • Understanding TPhP's effects on bone metabolism is crucial.

Purpose of the Study:

  • To elucidate the molecular mechanisms of TPhP-induced disruption of bone metabolism.
  • To identify key molecular targets and pathways affected by TPhP.
  • To assess the potential health risks associated with TPhP exposure.

Main Methods:

  • Network toxicology and molecular docking approaches were used.
  • Bioinformatic analyses included database searches (ChEMBL, STITCH, GeneCards, OMIM), PPI network construction (STRING, Cytoscape), and functional enrichment (GO, KEGG).
  • In vitro experiments with MC3T3-E1 osteoblasts validated findings.

Main Results:

  • 78 potential targets for TPhP in bone metabolism were identified.
  • Six key proteins (IGF1R, NR3C1, MAP3K1, BRAF, WNK4, CNR2) were highlighted, primarily linked to the MAPK signaling pathway.
  • TPhP inhibited osteoblast proliferation and migration, downregulating EMT-related proteins and target genes via MAPK signaling.

Conclusions:

  • TPhP disrupts bone metabolism by modulating critical proteins and signaling pathways.
  • The findings highlight potential health risks of TPhP exposure.
  • Further epidemiological and clinical studies are warranted.
Keywords:
MAPK signaling pathwaynetwork toxicologyosteoblastosteoporosistriphenyl phosphate (TPHP)

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