Secretion of specific metabolites and changes in miRNA expression in murine osteoblastic cells exposed in vitro to α‑radiation.

Abstract

Osteoblastic cells (OBCs) in bone marrow (BM) support hematopoietic stem/progenitor cells (HSPCs) by forming a regulatory niche through cytokine and metabolite secretion. Targeted α‑emitting radionuclide therapy, such as radium‑223 dichloride (²²³RaCl₂), is effective in treating bone metastases but frequently causes unpredictable hematologic toxicities. The underlying mechanism remains unclear. The present study hypothesized that α‑radiation alters the OBC secretome and miRNA expression, thereby modulating the BM microenvironment and influencing therapy response. The present study aimed to characterize proteomic, lipidomic and miRNA expression profiles in OBCs following α‑radiation exposure. Primary murine BM cells were differentiated into OBCs and irradiated with 0‑1 Gy of α‑radiation using a ²⁴¹Am source. Mass spectrometry was used to analyze intracellular proteins and lipids and miRNA expression was assessed by microarray analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment was performed using OmicsNet 2.0. α‑radiation markedly reduced OBC clonogenic survival and induced specific molecular alterations. α total of six proteins and several lipid species, particularly from the phosphatidylcholine family, showed significant alterations. miRNAs including miR‑1895, miR‑370‑3p and miR‑188‑5p were downregulated. Enrichment analysis revealed involvement in transcriptional regulation, apoptosis, glycerophospholipid metabolism and cytokine signaling. In conclusion, α‑radiation induced distinct proteomic, lipidomic and miRNA changes in OBCs, potentially affecting BM radiosensitivity. These molecules may serve as candidate biomarkers for predicting individual susceptibility to α‑emitting radionuclide therapy.