Impaired osteogenic differentiation of mesenchymal stem cells derived from bone marrow of patients with lower-risk myelodysplastic syndromes
Impaired osteogenic differentiation of mesenchymal stem cells derived from bone marrow of patients with lower-risk myelodysplastic syndromes
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低风险骨髓增生异常综合征患者骨髓间充质干细胞的成骨分化受损
DOI：
10.1007/s13277-013-1565-6
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发表时间：
2014-05-01
期刊：
影响因子：
--
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
骨髓增生异常综合征（MDS）的发病机制尚不完全清楚，造血微环境的不足可能是一个重要因素。间充质干细胞和成骨细胞是造血微环境的关键组成部分。本研究采用实时荧光定量PCR技术检测了58例不同疾病分期和亚型MDS患者骨髓间充质干细胞中多个成骨基因的表达，并定量动态比较了20例MDS患者骨髓间充质干细胞与8例正常对照骨髓间充质干细胞的成骨分化。在低危MDS未分化的MSCs中，参与成骨细胞早期分化过程的两个关键因子Osterix和RUNX2的mRNA水平显著降低。成骨诱导后，低危MDS碱性磷酸酶活性较低，茜素红S染色较弱，成骨分化标志物基因表达较低；但高危MDS正常。最后，在骨髓活检中，低风险MDS的成骨细胞数量明显减少。这些结果表明，来自低风险MDS的MSCs的成骨分化功能受损，表明它们在MDS中的基质支持不足。
The pathogenesis of myelodysplastic syndromes (MDS) has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. Mesenchymal stem cells (MSCs) and osteoblasts are key components of the hematopoietic microenvironment. Here, we measured the expression of multiple osteogenic genes in 58 MSCs from MDS patients with different disease stages and subtypes by real-time PCR and compared the osteogenic differentiation of MSCs from 20 MDS patients with those of MSCs from eight normal controls quantitatively and dynamically. The mRNA level of Osterix and RUNX2, two key factors involved in the early differentiation process toward osteoblasts, was significantly reduced in undifferentiated MSCs from lower-risk MDS. After osteogenic induction, lower-risk MDS showed lower alkaline phosphatase activity, less intense alizarin red S staining, and lower gene expression of osteogenic differentiation markers; however, higher-risk MDS was normal. Finally, in bone marrow biopsy, the number of osteoblasts was significantly decreased in lower-risk MDS. These results indicate that MSCs from lower-risk MDS have impaired osteogenic differentiation functions, suggesting their insufficient stromal support in MDS.