Monzen Satoru, Tatara Yota, Chiba Mitsuru, Mariya Yasushi, Wojcik Andrzej
Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan.
Department of Stress Response Science, Biomedical Research Center, Graduate School of Medicine, Hirosaki University, Hirosaki, Aomori 036‑8562, Japan.
Int J Mol Med. 2025 Oct;56(4). doi: 10.3892/ijmm.2025.5602. Epub 2025 Aug 1.
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 (RaCl), 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 Am 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.
骨髓中的成骨细胞（OBCs）通过分泌细胞因子和代谢产物形成调节性微环境来支持造血干/祖细胞（HSPCs）。靶向α发射放射性核素治疗，如二氯化镭（RaCl），对治疗骨转移有效，但经常导致不可预测的血液学毒性。其潜在机制仍不清楚。本研究假设α辐射会改变OBC的分泌组和miRNA表达，从而调节骨髓微环境并影响治疗反应。本研究旨在表征α辐射暴露后OBC中的蛋白质组学、脂质组学和miRNA表达谱。将原代小鼠骨髓细胞分化为OBCs，并使用锕源用0 - 1 Gy的α辐射进行照射。采用质谱分析细胞内蛋白质和脂质，并通过微阵列分析评估miRNA表达。使用OmicsNet 2.0进行京都基因与基因组百科全书通路富集分析。α辐射显著降低了OBC的克隆形成存活率并诱导了特定的分子改变。总共六种蛋白质和几种脂质种类，特别是来自磷脂酰胆碱家族的脂质，表现出显著变化。包括miR - 1895、miR - 370 - 3p和miR - 188 - 5p在内的miRNA被下调。富集分析显示参与转录调控、细胞凋亡、甘油磷脂代谢和细胞因子信号传导。总之，α辐射在OBCs中诱导了明显的蛋白质组学、脂质组学和miRNA变化，可能影响骨髓放射敏感性。这些分子可能作为预测个体对α发射放射性核素治疗易感性的候选生物标志物。
