Unveiling the Mechanisms of Bone Marrow Toxicity Induced by Lead Acetate Exposure

Lead (Pb), a widespread heavy metal, causes severe toxicity in human and animal organs (e.g., bone marrow), whereas the mechanisms of the bone marrow toxicity induced by Pb exposure are unclear. Hence, this study was designed to reveal the hub genes involved in Pb-induced bone marrow toxicity. GSE59894 dataset obtained from Gene Expression Omnibus (GEO) was composed of lead acetate (PbAc₂)-treated and control bone marrow samples. Totally 120 and 85 differentially expressed genes (DEGs) were identified on the 1st day, while 153 and 157 DEGs on the 3rd day in the bone marrow treated with 200 and 600 mg/kg of PbAc₂, respectively. Notably, a total of 28 and 32 overlapping DEGs were identified in the bone marrow on the 1st and 3rd day treated with PbAc₂, respectively. Biological process analysis suggested that the common DEGs were primarily participated in cell differentiation, the response to drug, xenobiotic stimulus, and organic cyclic compound. Pathway analysis demonstrated that the overlapping DEGs were primarily linked to PI3K-Akt, TGF-β, MAPK, and osteoclast differentiation signaling pathways. Moreover, the hub genes, including PLD2, DAPK1, ALB, TNF, FOS, CDKN1A, and TGFB3, might contribute to PbAc₂-induced bone marrow toxicity. Overall, our study offers an important insight into the molecular mechanisms of Pb-induced bone marrow toxicity.