Integrin-mediated interactions between human bone marrow stromal precursor cells and the extracellular matrix
Integrin-mediated interactions between human bone marrow stromal precursor cells and the extracellular matrix
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DOI：
10.1016/s8756-3282(00)00424-5
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发表时间：
2001-02-01
期刊：
影响因子：
4.1
通讯作者：
Robey, PG
中科院分区：
文献类型：
--
作者：
Gronthos, S;Simmons, PJ;Robey, PG
到目前为止，骨髓基质细胞和细胞外基质之间的确切相互作用，管理基质细胞的发展仍然不清楚。细胞表面粘附分子的整合素超家族代表了几乎所有细胞类型与不同细胞外基质组分相互作用的主要途径。在这项研究中，通过荧光激活细胞分选从正常人骨髓的STRO-1阳性部分中分离纯化的基质前体细胞群，然后测定它们在各种整合素配体存在下启动克隆形成生长的能力。骨髓来源的基质前体细胞显示与纤连蛋白、玻连蛋白和层粘连蛋白的差异生长，超过I型和III型胶原，但对IV型胶原蛋白显示出相似的亲和力。发现整联蛋白异二聚体α（1）β（1）、α（2）β（1）、α（5）β（1）、α（6）β（1）、α（v）β（3）和α（v）β（5）与CFU-F的细胞表面上的STRO-1抗原共表达，使用双色分析。此外，只有一部分基质前体表达整合素α（4）β（1），而不能检测到可测量水平的整合素α（3）β（1）。随后使用针对不同整合素α/β异二聚体的功能性阻断抗体进行的粘附研究表明，基质细胞在胶原蛋白、层粘连蛋白和纤连蛋白上的生长是由多种β（1）整合素介导的。相反，在玻连蛋白存在下的克隆效率部分由α v β 3介导。当在骨诱导条件下培养人骨髓基质细胞时，它们在体外形成矿化基质的能力在β（1）整联蛋白亚基的功能性阻断单克隆抗体存在下显著降低，这项研究的结果表明，β（1）整联蛋白似乎是基质前体细胞利用的主要粘附受体亚家族表面。此外，这些数据表明β（1）整合素亚家族在基质前体细胞发育成功能性成骨细胞样细胞的过程中可能发挥作用。(Bone 28：174 - 181; 2001）（C）Elsevier Science Inc. All rights reserved.
To date, the precise interactions between bone marrow stromal cells and the extracellular matrix that govern stromal cell development remain unclear. The integrin super-family of cell-surface adhesion molecules represents a major pathway used by virtually all cell types to interact with different extracellular matrix components. In this study, purified populations of stromal precursor cells were isolated from the STRO-1-positive fraction of normal human marrow, by fluoresence-activated cell sorting, and then assayed for their ability to initiate clonogenic growth in the presence of various integrin ligands, Bone marrow-derived stromal progenitors displayed differential growth to fibronectin, vitronectin, and laminin, over collagen types I and III, but showed a similar affinity fur collagen type IV, The integrin heterodimers alpha (1)beta (1), alpha (2)beta (1), alpha (5)beta (1), alpha (6)beta (1), alpha (v)beta (3), and alpha (v)beta (5) were found to coexpress with the STRO-1 antigen on the cell surface of CFU-F, using dual-color analysis. Furthermore, only a proportion of stromal precursors expressed the integrin alpha (4)beta (1), while no measurable levels of the integrin alpha (3)beta (1) could be detected. Subsequent adhesion studies using functional blocking antibodies to different integrin alpha/beta heterodimers showed that stromal cell growth on collagen, laminin, and fibronectin was mediated by multiple beta (1) integrins, In contrast, cloning efficiency in the presence of vitronectin was mediated in part by alphav beta3, When human marrow stromal cells were cultured under osteoinductive conditions, their ability to form a mineralized matrix in vitro was significantly diminished in the presence of a functional blocking monoclonal antibody to the beta (1) integrin subunit, The results of this study indicate that beta (1) integrins appear to be the predominant adhesion receptor subfamily utilized by stromal precursor cells to adhere and proliferate utilizing matrix glycoproteins commonly found in the bone marrow microenvironment and bone surfaces. Furthermore, these data suggest a possible role for the beta (1) integrin subfamily during the development of stromal precursor tells into functional osteoblast-like cells. (Bone 28: 174-181; 2001) (C) 2001 by Elsevier Science Inc. All rights reserved.