摘 要：摘 要：转化生长因子-b(TGF-b)是一个包括数十种TGF-bs、骨形态发生蛋白(BMPs)等配体在内的生长因子超家族，在哺乳动物整体和组织器官发育过程中具有广泛而重要的功能。Smad4是细胞内TGF-b信号通路的核心信号转导分子。为了深入研究Smad4介导的TGF-b信号在骨骼发育过程中的生理功能，我们利用转基因技术研制了软骨细胞、肥大型软骨细胞和成骨细胞分别特异性表达Cre重组酶的转基因小鼠，利用条件基因敲除技术研制了不同类型骨骼细胞Smad4基因敲除的小鼠模型。表型分析结果揭示了Smad4在软骨细胞增殖和分化、骨重塑以及稳态维持过程中的功能以及相关的分子机制，为理解人类相关骨骼疾病的发生及其机理提供了新的线索。
关键词：Smad4；软骨内成骨；骨重塑；条件基因敲除
中图分类号：R318；Q983.3 文献标识码：A
Abstract: Abstract: Transforming growth factor-b (TGF-b) is a large family of cytokines consisting of several tens of ligands including TGF-bs and bone morphogenetic proteins (BMPs). It plays very important and diverse functions during mammalian development and organogenesis. Smad4 is a central intracellular mediator of TGF-b signaling. To further study the physiological function of Smad4 mediated TGF-b signals in bone development, we have generated bone tissue specific Cre transgenic mice which expressed the Cre recombinase specifically in chondrocyte, hypertrophic chondrocyte or osteoblast respectively, and bone tissue specific Smad4 gene knockout mice. Phenotype analyses revealed the functions of Smad4 and related molecular mechanisms in chondrocyte proliferation and differentiation, bone remodeling and homeostasis, and provided new clues for understanding mechanisms underlying related human skeletal diseases.
Key words: Smad4; endochondral ossification; bone remodeling; conditional gene knockout
