Effects of continuous dexamethasone treatment on differentiation capabilities of bone marrow-derived mesenchymal cells
Effects of continuous dexamethasone treatment on differentiation capabilities of bone marrow-derived mesenchymal cells
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DOI：
10.1016/j.bone.2007.06.022
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发表时间：
2007-10-01
期刊：
影响因子：
4.1
通讯作者：
Shinomiya, Kenichi
中科院分区：
文献类型：
--
作者：
Oshina, Hidekazu;Sotome, Shinichi;Shinomiya, Kenichi
人骨髓源性间充质细胞（hBMMC）来源于骨髓中的细胞群，并且能够沿沿着多个间充质谱系分化。为了将hBMMC分化为成骨细胞、脂肪细胞和软骨细胞，地塞米松已被用作分化试剂。我们假设地塞米松会增强骨髓基质细胞对其他分化试剂的反应性，而不是定义谱系。本研究探讨了100 nM地塞米松连续处理对骨髓基质细胞分化为三种不同谱系的影响。与仅用地塞米松处理的hBMMCs相比，在分化培养过程中，用100 nM地塞米松连续处理的hBMMCs表现出更高的成骨标志物mRNA表达水平和更高的成骨集落形成单位测定阳性率。此外，在骨诱导实验模型中，连续地塞米松治疗增强了猴源性BMMCs在额外骨骼部位的骨形成能力。此外，连续地塞米松处理的hBMMCs形成更大的软骨形成颗粒，并表达更高水平的SOX 9比对照BMMCs。同样，基于mRNA水平和集落形成单位分析，连续地塞米松处理促进成脂分化。研究表明，地塞米松选择性地诱导某些被认为分化能力差的hBMMC群体的凋亡。(C)2007年爱思唯尔公司All rights reserved.
Human bone marrow-derived mesenchymal cells (hBMMCs) originate from cell populations in the bone marrow and are capable of differentiating along multiple mesenchymal lineages. To differentiate hBMMCs into osteoblasts, adipocytes and chondrocytes, dexamethasone has been used as a differentiation reagent. We hypothesized that dexamethasone would augment the responsiveness of BMMCs to other differentiation reagents and not define the lineage. This study investigated the effect of continuous treatment with 100 nM dexamethasone on the differentiation of BMMCs into three different lineages.hBMMCs Cultured with continuous dexamethasone treatment (100 nM) exhibited higher mRNA expression levels of osteogenic markers and higher positive rates of colony forming unit assays for osteogenesis compared to hBMMCs treated with dexamethasone only during the differentiation culture. Furthermore, continuous dexamethasone treatment augmented bone formation capability of monkey-derived BMMCs in a bone induction experimental model at an extra skeletal site. In addition, continuously dexamethasone-treated hBMMCs formed larger chondrogenic pellets and expressed SOX9 at higher level than the control BMMCs. Likewise, continuous dexamethasone treatment facilitated adipogenic differentiation based on mRNA level and colony forming unit analysis.To investigate the mechanism of the augmentation of differentiation, further studies on apoptosis were conducted. The studies indicated that dexamethasone selectively induced apoptosis of some populations of hBMMCs which were thought to have poor differentiation capability. (C) 2007 Elsevier Inc. All rights reserved.