Bendall Andrew J, Hu Gezhi, Levi Giovanni, Abate-Shen Cory
Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Int J Dev Biol. 2003 Jun;47(5):335-44.
Endochondral ossification, in which cartilaginous templates are progressively replaced by marrow and bone, represents the dominant mode of development of the axial and appendicular skeleton of vertebrates. Chondrocyte differentiation within the cartilaginous core of these skeletal elements is tightly regulated, both spatially and temporally. Here, we describe the expression of Dlx5 in the cartilaginous core of limb skeletal elements in chicken and mouse embryos. We find that Dlx5 is one of the earliest genes expressed in condensing limb mesenchyme that will give rise to the limb skeleton. Later, when proliferating and differentiating chondrocytes are found in spatially distinct regions of the cartilaginous model, Dlx5 is expressed in the zone of hypertrophy and in proliferating chondrocytes that are poised to differentiate. Consistent with this pattern of expression, we show that forced expression of Dlx5 potentiates early and late chondrocyte differentiation and inhibits proliferation in cultured cells. Examination of the limbs of mutant Dlx5 mouse embryos revealed that they displayed a delay in chondrocyte maturation compared with wild type littermates. Taken together, our data reveal a positive role for Dlx5 during multiple stages of chondrocyte differentiation and, along with previous studies of Dlx5 and osteogenesis, identify Dlx5 as a general regulator of differentiation in the mouse skeleton.
软骨内成骨是指软骨模板逐渐被骨髓和骨替代的过程，它是脊椎动物轴骨和附肢骨骼发育的主要模式。这些骨骼结构的软骨核心内的软骨细胞分化在空间和时间上都受到严格调控。在这里，我们描述了Dlx5在鸡和小鼠胚胎肢体骨骼结构软骨核心中的表达情况。我们发现Dlx5是在即将形成肢体骨骼的凝聚肢体间充质中最早表达的基因之一。之后，当在软骨模型的不同空间区域发现增殖和分化的软骨细胞时，Dlx5在肥大区以及准备分化的增殖软骨细胞中表达。与这种表达模式一致，我们表明在培养细胞中强制表达Dlx5可增强早期和晚期软骨细胞分化并抑制增殖。对Dlx5突变小鼠胚胎的肢体检查显示，与野生型同窝小鼠相比，它们的软骨细胞成熟出现延迟。综上所述，我们的数据揭示了Dlx5在软骨细胞分化的多个阶段中具有积极作用，并且与之前关于Dlx5和成骨作用的研究一起，确定Dlx5是小鼠骨骼分化的一般调节因子。
