CCN3 and bone marrow cells
CCN3 and bone marrow cells
复制标题
DOI：
10.1007/s12079-009-0059-1
复制
发表时间：
2009-06-01
影响因子：
4.1
通讯作者：
Yamaguchi, Akira
中科院分区：
文献类型：
--
作者：
Katsube, Ken-ichi;Ichikawa, Saki;Yamaguchi, Akira
从发育早期起，CCN3在多种组织中都有表达。然而，在小鼠中有一种功能丧失(CCN3 del VWC结构域-/-)表现出轻微的异常，这表明CCN3作为一个单基因可能不是正常胚胎发生的关键基因。随着对造血干细胞和慢性髓系白血病细胞的研究，CCN3在骨髓环境中的重要性逐渐被认识到。CCN3在骨髓中的表达已被多项研究否认，但我们发现，尽管CCN3阳性的基质细胞和造血细胞数量很少，但我们发现了一种新的抗体。我们研究了CCN3在培养的骨髓间充质干细胞中的表达模式，发现它对成骨分化有偏好。通过对成骨间充质干细胞系Kusa-A1的体外实验分析，我们发现CCN3通过两种不同的途径下调成骨：抑制BMP和刺激Notch。Kusa细胞分泌的CCN3在分离培养中对成骨细胞的分化有抑制作用，提示CCN3活性的旁分泌方式。CCN3也可能影响造血干细胞的细胞外环境。
CCN3 expression was observed in a broad variety of tissues from the early stage of development. However, a kind of loss of function in mice (CCN3 del VWC domain -/-) demonstrated mild abnormality, which indicates that CCN3 may not be critical for the normal embryogenesis as a single gene. The importance of CCN3 in bone marrow environment becomes to be recognized by the studies of hematopoietic stem cells and Chronic Myeloid Leukemia cells. CCN3 expression in bone marrow has been denied by several investigations, but we found CCN3 positive stromal and hematopoietic cells at bone extremities with a new antibody although they are a very few populations. We investigated the expression pattern of CCN3 in the cultured bone marrow derived mesenchymal stem cells and found its preference for osteogenic differentiation. From the analyses of in vitro experiment using an osteogenic mesenchymal stem cell line, Kusa-A1, we found that CCN3 downregulates osteogenesis by two different pathways; suppression of BMP and stimulation of Notch. Secreted CCN3 from Kusa cells inhibited the differentiation of osteoblasts in separate culture, which indicates the paracrine manner of CCN3 activity. CCN3 may also affect the extracellular environment of the niche for hematopoietic stem cells.