Iron-lead mixed exposure causes bone damage in mice: A multi-omics analysis

Area of Science:

• Environmental toxicology
• Bone biology
• Multi-omics research

Background:

• Osteoporosis is influenced by essential and toxic metal intake.
• While single metal effects on bone are known, combined Fe and Pb exposure mechanisms remain unclear.
• Metals are often ingested together, necessitating research into their synergistic effects on bone health.

Purpose of the Study:

• To elucidate the molecular mechanisms of bone damage induced by combined iron (Fe) and lead (Pb) exposure.
• To investigate the role of proteomics and metabolomics in understanding Fe and Pb-induced bone injury.
• To identify key molecular players and pathways involved in Fe and Pb-mediated bone damage.

Main Methods:

• Combined proteomics and metabolomics analysis to explore molecular mechanisms.
• Identification of differential proteins and metabolites associated with Fe and Pb exposure.
• Enrichment analysis of signaling pathways and biological processes.

Main Results:

• Proteomic and metabolomic analyses revealed significant enrichment in the JAK-STAT signaling pathway, inflammatory bowel disease (IBD), and osteoclast differentiation.
• Specific molecules such as Fpr2, Lifr, Lisofylline, 7-Ketocholesterol, and LacCer were implicated in Fe and Pb-mediated bone injury.
• Findings suggest a dual mechanism involving in situ osteoclast activation via JAK-STAT signaling and indirect effects through the gut-bone axis.

Conclusions:

• Mixed Fe and Pb exposure promotes bone damage, potentially through osteoclast activation.
• The JAK-STAT signaling pathway and gut-bone axis are likely involved in Fe and Pb-induced bone injury.
• Changes in inflammatory levels may mediate osteoclast proliferation and subsequent bone damage from combined metal exposure.