@article{CHEN2026, 
author = {Yanzhou CHEN and Yunxing LI and Bowen ZHAGN and Yunqiao LI and Yang LÜ and Tao FAN and Caiping XU and Yanhua LI},
title = {Effects of SB4 on mitigation of radiation-induced mouse bone marrow hematopoietic stem and progenitor cell injury},
year = {2026},
journal = {Military Medical Sciences},
volume = {50},
number = {5},
pages = {334-341},
keywords = {hematopoietic stem and progenitor cells, BMP4 signaling agonist SB4, radiation injury, antioxidative stress},
url = {https://www.sciopen.com/article/10.7644/j.issn.1674-9960.2025-00285},
doi = {10.7644/j.issn.1674-9960.2025-00285},
abstract = {ObjectiveTo investigate whether SB4, a bone morphogenetic protein 4 (BMP4) signaling agonist, can alleviate ionizing radiation-induced damage to mouse bone marrow hematopoietic stem/progenitor cells (HSPCs). MethodsMouse bone marrow lineage-negative (Lin-) cells were isolated and cultured in vitro. The optimal concentration of SB4 was determined by detecting intracellular phosphorylated mothers against decapentaplegic homolog 1/5/9 (p-SMAD1/5/9) expressions via flow cytometry and assessing cell viability via acridine orange/propidium iodide (AO/PI) staining. An in vitro ionizing radiation (IR) injury model was established by exposing Lin- cells to 3 Gy X-ray irradiation. Cells were divided into the irradiation alone group (IR-SB4 group) and the SB4 pretreatment followed by irradiation group (IR+SB4 group). On day 1 post-irradiation, flow cytometry was used to analyze the proportion and number of HSPCs and hematopoietic stem cells (HSCs). The percentage of γ-H2A histone family member X (γ-H2AX)-positive cells, levels of reactive oxygen species (ROS), and cysteinyl aspartate-specific protease 3 (caspase-3) expressions in HSCs were also determined. Real-time quantitative PCR (qPCR) was used to detect the mRNA expression levels of antioxidant genes and the anti-apoptotic genes in HSPCs from both groups. ResultsThe BMP4 signaling agonist SB4 effectively increased the phosphorylation of SMAD1/5/9 in mouse bone marrow hematopoietic cells, and 1 μmol/L was identified as the optimal concentration for HSPCs. Compared with the IR-SB4 group, the proportions and numbers of HSPCs and HSCs were significantly larger in the IR+SB4 group, along with a lower γ-H2AX-positive rate, reduced ROS accumulation, and downregulated caspase-3 expressions in HSCs. Meanwhile, the mRNA expression levels of key genes involved in antioxidative stress and anti-apoptotic pathways in HSPCs were upregulated. ConclusionSB4 can alleviate ionizing radiation-induced damage to mouse HSPCs. The underlying mechanism is possibly associated with the activation of SMAD1/5/9 phosphorylation and the upregulation of antioxidative stress and anti-apoptotic gene expressions in HSPCs.}
}