Osteogenic differentiation of mesenchymal stem cells from dental bud: Role of integrins and cadherins
Osteogenic differentiation of mesenchymal stem cells from dental bud: Role of integrins and cadherins
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DOI：
10.1016/j.scr.2015.09.011
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发表时间：
2015-11-01
影响因子：
1.2
通讯作者：
Mori, Giorgio
中科院分区：
文献类型：
--
作者：
Di Benedetto, Adriana;Brunetti, Giacomina;Mori, Giorgio
一些研究报道了间充质干细胞（MSCs）在组织修复和再生中的有益作用。成体干细胞的新来源不断涌现；牙组织已被确定为产后间充质干细胞的来源。牙芽是牙齿的未成熟前体，很容易接近，我们在本研究中发现它可以产生大量的细胞，>= 95%表达间充质硬度制造细胞和成骨能力。因此，这些细胞可以被定义为牙芽干细胞（DBSCs），代表了一个有希望的骨再生来源的口颌和其他系统。细胞与细胞外基质（ECM）和邻近细胞的相互作用对组织形态发生和结构至关重要；这种相互作用分别由整合素和钙粘蛋白介导。我们对这些粘附受体的表达进行了表征，并检查了它们在成骨分化过程中的模式。我们的数据表明，N-cadherin和cadherin-11在未分化的DBSCs中表达，其表达在成骨过程中发生变化（分别减少和增加），而E-cadherin和P-cadherin在DBSCs中的表达非常低，在分化过程中没有变化。这种表达模式反映了DBSCs的间充质起源，证实了其成骨细胞样特征。另一方面，成骨刺激诱导单个亚单位α V、β 3、α 5的上调，并形成整合素受体α 5 β 1和α V β 3。当细胞生长在纤维连接蛋白（FN）、玻璃体连接蛋白（VTN）和骨桥蛋白（OPN）上时，DBSCs向成骨细胞谱系的分化增强，这些ECM糖蛋白含有整合素结合序列RGD基序。此外，我们确定了整合素α V β 3在MSCs向成骨细胞谱系的转变过程中起着至关重要的作用，而整合素α 5 β 1似乎是可有可无的。这些数据表明，具有这种ECM蛋白的生物材料的功能化将改善从牙齿干细胞开始的骨重建治疗。(C) 2015年作者。Elsevier B.V.出版
Several studies have reported the beneficial effects of mesenchymal stem cells (MSCs) in tissue repair and regeneration. New sources of stem cells in adult organisms are continuously emerging; dental tissues have been identified as a source of postnatal MSCs. Dental bud is the immature precursor of the tooth, is easy to access and we show in this study that it can yield a high number of cells with >= 95% expression of mesenchymal sternness makers and osteogenic capacity. Thus, these cells can be defined as Dental Bud Stem Cells (DBSCs) representing a promising source for bone regeneration of stomatognathic as well as other systems. Cell interactions with the extracellular matrix (ECM) and neighboring cells are critical for tissue morphogenesis and architecture; such interactions are mediated by integrins and cadherins respectively. We characterized DBSCs for the expression of these adhesion receptors and examined their pattern during osteogenic differentiation. Our data indicate that N-cadherin and cadherin-11 were expressed in undifferentiated DBSCs and their expression underwent changes during the osteogenic process (decreasing and increasing respectively), while expression of E-cadherin and P-cadherin was very low in DBSCs and did not change during the differentiation steps. Such expression pattern reflected the mesenchymal origin of DBSCs and confirmed their osteoblast-like features. On the other hand, osteogenic stimulation induced the upregulation of single subunits, alpha V, beta 3, alpha 5, and the formation of integrin receptors alpha 5 beta 1 and alpha V beta 3. DBSCs differentiation toward osteoblastic lineage was enhanced when cells were grown on fibronectin (FN), vitronectin (VTN), and osteopontin (OPN), ECM glycoproteins which contain an integrin-binding sequence, the RGD motif. In addition we established that integrin alpha V beta 3 plays a crucial role during the commitment of MSCs to osteoblast lineage, whereas integrin alpha 5 beta 1 seems to be dispensable. These data suggest that functionalization of biomaterials with such ECM proteins would improve bone reconstruction therapies starting from dental stem cells. (C) 2015 The Authors. Published by Elsevier B.V.