Dlx5 is a positive regulator of chondrocyte differentiation during endochondral ossification
Dlx5 is a positive regulator of chondrocyte differentiation during endochondral ossification
复制标题
DOI：
10.1006/dbio.2002.0862
复制
发表时间：
2002-12-15
影响因子：
2.7
通讯作者：
Kosher, RA
中科院分区：
文献类型：
--
作者：
Ferrari, D;Kosher, RA
软骨模型生成后形成肢体骨骼的软骨内骨化过程依赖于软骨细胞成熟的精确调节程序。在这里，我们表明，含有同源框的基因D1x5的表达在软骨细胞成熟的发病过程中，未成熟的增殖软骨细胞转化为有丝分裂后肥大的软骨细胞，在成熟过程中的关键步骤。此外，逆转录病毒的D1x5的错误表达过程中的鸡肢体的骨骼元素的分化在体内的结果在严重缩短的骨骼元素的形成，含有过量的肥大软骨细胞延伸到异位区域，包括网站通常由未成熟的软骨细胞占据。组织学上可检测到的肥大成熟程度的扩大伴随着软骨细胞成熟的分子标志物（特别是X型胶原和骨桥蛋白）的表达的扩大和上调的结构域，以及矿化软骨基质的扩大，这是终末肥大分化的特征。此外，D1x5错误表达显著降低软骨细胞增殖，同时促进肥大成熟。综上所述，这些结果表明，D1x5是软骨细胞成熟的正调控因子，并表明它至少部分地通过促进未成熟增殖软骨细胞转化为肥大软骨细胞来调控该过程。D1x5的逆转录病毒错误表达也增强骨膜骨的形成，骨膜骨来源于围绕软骨模型骨干的表达D1x5的软骨膜。这表明，D1x5可能参与调节成骨细胞分化，以及软骨细胞成熟，在endochondrialossification。(C)2002年爱思唯尔科学（美国）。
The process of endochondral ossification in which the bones of the limb are formed after generation of cartilage models is dependent on a precisely regulated program of chondrocyte maturation. Here, we show that the homeobox-containing gene D1x5 is expressed at the onset of chondrocyte maturation during the conversion of immature proliferating chondrocytes into postmitotic hypertrophying chondrocytes, a critical step in the maturation process. Moreover, retroviral misexpression of D1x5 during differentiation of the skeletal elements of the chick limb in vivo results in the formation of severely shortened skeletal elements that contain excessive numbers of hypertrophying chondrocytes which extend into ectopic regions, including sites normally occupied by immature chondrocytes. The expansion in the extent of hypertrophic maturation detectable histologically is accompanied by expanded and upregulated domains of expression of molecular markers of chondrocyte maturation, particularly type X collagen and osteopontin, and by expansion of mineralized cartilage matrix, which is characteristic of terminal hypertrophic differentiation. Furthermore, D1x5 misexpression markedly reduces chondrocyte proliferation concomitant with promoting hypertrophic maturation. Taken together, these results indicate that D1x5 is a positive regulator of chondrocyte maturation and suggest that it regulates the process at least in part by promoting conversion of immature proliferating chondrocytes into hypertrophying chondrocytes. Retroviral misexpression of D1x5 also enhances formation of periosteal bone, which is derived from the D1x5-expressing perichondrium that surrounds the diaphyses of the cartilage models. This suggests that D1x5 may be involved in regulating osteoblast differentiation, as well as chondrocyte maturation, during endochondral ossification. (C) 2002 Elsevier science (USA).