Clinical significance of hyaluronan levels and its pro-osteogenic effect on mesenchymal stromal cells in myelodysplastic syndromes.
Clinical significance of hyaluronan levels and its pro-osteogenic effect on mesenchymal stromal cells in myelodysplastic syndromes.
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骨髓增生异常综合征中透明质酸水平及其对间充质基质细胞的促成骨作用的临床意义
DOI：
10.1186/s12967-018-1614-4
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发表时间：
2018-08-24
影响因子：
7.4
通讯作者：
Chang CK
中科院分区：
文献类型：
--
作者：
Fei CM;Guo J;Zhao YS;Zhao SD;Zhen QQ;Shi L;Li X;Chang CK
透明质酸（HA）是细胞外基质的主要成分，已被证实在肿瘤进展中发挥关键作用。然而，透明质酸在骨髓增生异常综合征（MDS）中是否发挥作用仍不清楚。
本研究共纳入82例MDS患者和28名健康供者。我们首先通过放射免疫分析法检测MDS患者骨髓（BM）血清中透明质酸的水平。然后测定MDS患者骨髓间充质基质细胞（MSC）和单核细胞中透明质酸的生成以及透明质酸合酶（HAS）基因的表达。最后，研究透明质酸对MSC成骨分化的影响。
与正常对照组相比，高危MDS患者骨髓血清中透明质酸水平升高。同时，骨髓血清透明质酸水平高的患者中位生存期明显短于透明质酸水平低的患者。此外，MDS患者尤其是高危MDS患者的MSC分泌的透明质酸水平升高。另外，高危MDS患者的MSC中HAS - 2 mRNA表达也上调。进一步研究发现，骨髓血清透明质酸水平高的MDS患者来源的MSC具有更强的成骨分化潜能。而且，在包被透明质酸的表面培养的MSC表现出增强的成骨分化能力。
我们的研究结果表明，骨髓血清透明质酸水平升高与MDS不良临床结局相关。透明质酸诱导的MSC更好的成骨分化可能与MDS的发病机制有关。
Hyaluronan (HA), a major component of the extracellular matrix, has been proven to play a crucial role in tumor progression. However, it remains unknown whether HA exerts any effects in myelodysplastic syndromes (MDS). A total of 82 patients with MDS and 28 healthy donors were investigated in this study. We firstly examined the bone marrow (BM) serum levels of HA in MDS by radioimmunoassay. Then we determined HA production and hyaluronan synthase (HAS) gene expression in BM mesenchymal stromal cells (MSC) and mononuclear cells derived from MDS patients. Finally, we investigated the effects of HA on osteogenic differentiation of MSC. The BM serum levels of HA was increased in higher-risk MDS patients compared to normal controls. Meanwhile, patients with high BM serum HA levels had significantly shorter median survival than those with low HA levels. Moreover, the HA levels secreted by MSC was elevated in MDS, especially in higher-risk MDS. In addition, HAS-2 mRNA expression was also up-regulated in higher-risk MDS-MSC. Furthermore, we found that MSC derived from MDS patients with high BM serum HA levels had better osteogenic differentiation potential. Moreover, MSC cultured in HA-coated surface presented enhanced osteogenic differentiation ability. Our results show that elevated levels of BM serum HA are related to adverse clinical outcome in MDS. Better osteogenic differentiation of MSC induced by HA may be implicated in the pathogenesis of MDS.
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影响因子：
--
作者：
Shigeeda W;Shibazaki M;Yasuhira S;Masuda T;Tanita T;Kaneko Y;Sato T;Sekido Y;Maesawa C
通讯作者：
Maesawa C
影响因子：
2.6
作者：
Li AJ;Calvi LM
通讯作者：
Calvi LM
影响因子：
20.3
作者：
Dahl, IMS;Turesson, I;Lilja, K
通讯作者：
Lilja, K
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
影响因子：
--
作者：
Fei, Chengming;Zhao, Youshan;Chang, Chunkang
通讯作者：
Chang, Chunkang
影响因子：
20.3
作者：
Greenberg, P;Cox, C;Bennett, J
通讯作者：
Bennett, J