The susceptive alendronate-treatment timing and dosage for osteogenesis enhancement in human bone marrow-derived stem cells.
The susceptive alendronate-treatment timing and dosage for osteogenesis enhancement in human bone marrow-derived stem cells.
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DOI：
10.1371/journal.pone.0105705
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ho ML
中科院分区：
文献类型：
--
作者：
Chang CH;Wang CZ;Chang JK;Hsu CY;Ho ML
最近的研究表明，阿仑膦酸钠增强成骨细胞和人骨髓源性干细胞的成骨作用。然而，时间和剂量依赖性的影响，铝对hBMSCs的成骨分化和细胞毒性仍然不确定。在本研究中，我们探讨了hBMSCs的有效剂量范围和时间。根据以下组用不同剂量（1、5和10 μM）的Aln处理hBMSC：A组在骨培养基的前5天用Aln处理，B、C和D组在骨诱导培养基的第一、第二和最后5天处理，E组在整个实验中处理。用茜素红S染色法和MTT比色法检测矿化程度和细胞毒性。此外，还研究了B组中补充法呢基焦磷酸和香叶基香叶基焦磷酸的逆转作用。结果显示，Aln处理A、B和E组均能促进hBMSC矿化，且呈剂量依赖性，其中以B和E组作用最明显。在B、C和E组中，高剂量的Aln在促进矿化的同时也引起细胞毒性。FPP或GGPP的补充分别部分或完全逆转了AlN诱导的矿化。此外，FPP或GGPP的加入也消除了AlN诱导的细胞毒性。我们证明了hBMSCs在成骨分化的起始阶段对5 μM Aln敏感，10 μM剂量具有细胞毒性。
Recent studies indicated that alendronate enhanced osteogenesis in osteoblasts and human bone marrow-derived stem cells. However, the time- and dose-dependent effects of Aln on ostegenic differentiation and cytotoxicity of hBMSCs remain undefined. In present study, we investigated the effective dose range and timing of hBMSCs. hBMSCs were treated with various Aln doses (1, 5 and 10 µM) according to the following groups: group A was treated with Aln during the first five days of bone medium, groups B, C and D were treated during the first, second, and final five days of osteo-induction medium and group E was treated throughout the entire experiment. The mineralization level and cytotoxicity were measured by quantified Alizarin Red S staining and MTT assay. In addition, the reversal effects of farnesyl pyrophosphate and geranylgeranyl pyrophosphate replenishment in group B were also investigated. The results showed that Aln treatment in groups A, B and E enhanced hBMSC mineralization in a dose-dependent manner, and the most pronounced effects were observed in groups B and E. The higher dose of Aln simultaneously enhanced mineralization and caused cytotoxicity in groups B, C and E. Replenishment of FPP or GGPP resulted in partial or complete reverse of the Aln-induced mineralization respectively. Furthermore, the addition of FPP or GGPP also eliminated the Aln-induced cytotoxicity. We demonstrated that hBMSCs are susceptible to 5 µM Aln during the initiation stage of osteogenic differentiation and that a 10 µM dose is cytotoxic.
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影响因子：
6.2
作者：
Luckman, SP;Hughes, DE;Rogers, MJ
通讯作者：
Rogers, MJ
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Hoemann, C. D.;El-Gabalawy, H.;McKee, M. D.
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作者：
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Mönkkönen, J