Senescence of bone marrow mesenchymal stromal cells is accompanied by activation of p53/p21 pathway in myelodysplastic syndromes
Senescence of bone marrow mesenchymal stromal cells is accompanied by activation of p53/p21 pathway in myelodysplastic syndromes
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骨髓增生异常综合征中骨髓间充质基质细胞的衰老伴随着p53/p21通路的激活
DOI：
10.1111/ejh.12385
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发表时间：
2014-12-01
影响因子：
3.1
通讯作者：
Chang, Chunkang
中科院分区：
文献类型：
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作者：
Fei, Chengming;Zhao, Youshan;Chang, Chunkang
骨髓间充质基质细胞（BMMSCs）在骨髓增生异常综合征（MDS）发病机制中的作用引起了争议。在这项研究中，我们证实来自MDS患者的BMMSCs表现出明显的衰老特征，其特征是细胞大小增加，增殖和集落形成潜力下降，细胞骨架改变，衰老相关的β -半乳糖苷酶（SA - β - Gal）活性增加。有趣的是，凋亡实验结果显示MDS患者的凋亡细胞百分比非常低，与正常对照组差异不显著。此外，细胞化学染色和RUNX2表达减少表明，低风险而非高风险MDS的骨髓间充质干细胞成骨分化潜力受损。此外，来自MDS患者的骨髓间充质干细胞造血支持功能受损。此外，在调节BMMSCs衰老进程中起重要作用的p53和p21的表达显著增加，而p16和pRb的表达水平在MDS患者的BMMSCs中没有变化。综上所述，我们的综合分析表明，来自MDS患者的BMMSCs表现出衰老行为，p53/p21通路的激活可能在衰老过程中发挥了重要作用。
The contribution of bone marrow mesenchymal stromal cells (BMMSCs) to the pathogenesis of myelodysplastic syndrome (MDS) has created controversies. In this study, we confirmed that BMMSCs from MDS patients showed prominent features of senescence, which were characterized by increased cell size, decreased proliferation and colony‐forming potential, alteration of cytoskeleton, and increased senescence‐associated β‐galactosidase (SA‐β‐Gal) activity. Interestingly, the apoptosis assay results showed that the percentage of apoptosis cells was very low and the difference was not significant between MDS patients and normal controls. Moreover, the osteogenic differentiation potential of BMMSCs from lower risk but not higher risk MDS was impaired, indicated by cytochemical stainings and reduced expressions of RUNX2. In addition, BMMSCs from MDS patients had impaired hematopoietic supporting function. Furthermore, the expression of p53 and p21 which played an important role in regulating the senescence progress of BMMSCs was significantly increased, whereas levels of p16 and pRb expression were not changed in the BMMSCs from MDS patients. Taken together, our comprehensive analysis shows that BMMSCs from MDS patients exhibited senescent behavior and activation of p53/p21 pathway probably played an important role in the senescence process.