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发育性软骨形成过程中的形态发生和调节机制:软骨组织工程的新范式

Morphogenetic and regulatory mechanisms during developmental chondrogenesis: new paradigms for cartilage tissue engineering.

作者信息

Quintana Lluís, zur Nieden Nicole I, Semino Carlos E

机构信息

Tissue Engineering Division, Department of Bioengineering, IQS-Ramon Llull University, Barcelona, Spain.

出版信息

Tissue Eng Part B Rev. 2009 Mar;15(1):29-41. doi: 10.1089/ten.teb.2008.0329.

Abstract

Cartilage is the first skeletal tissue to be formed during embryogenesis leading to the creation of all mature cartilages and bones, with the exception of the flat bones in the skull. Therefore, errors occurring during the process of chondrogenesis, the formation of cartilage, often lead to severe skeletal malformations such as dysplasias. There are hundreds of skeletal dysplasias, and the molecular genetic etiology of some remains more elusive than of others. Many efforts have aimed at understanding the morphogenetic event of chondrogenesis in normal individuals, of which the main morphogenetic and regulatory mechanisms will be reviewed here. For instance, many signaling molecules that guide chondrogenesis--for example, transforming growth factor-beta, bone morphogenetic proteins, fibroblast growth factors, and Wnts, as well as transcriptional regulators such as the Sox family--have already been identified. Moreover, extracellular matrix components also play an important role in this developmental event, as evidenced by the promotion of the chondrogenic potential of chondroprogenitor cells caused by collagen II and proteoglycans like versican. The growing evidence of the elements that control chondrogenesis and the increasing number of different sources of progenitor cells will, hopefully, help to create tissue engineering platforms that could overcome many developmental or degenerative diseases associated with cartilage defects.

摘要

软骨是胚胎发育过程中形成的第一种骨骼组织,除颅骨扁骨外,所有成熟软骨和骨骼均由此发育而来。因此,软骨形成过程中出现的错误,即软骨的形成过程,常常会导致严重的骨骼畸形,如发育异常。目前已知的骨骼发育异常有数百种,其中一些的分子遗传病因比其他的更难捉摸。许多研究致力于了解正常个体软骨形成的形态发生过程,本文将对此主要的形态发生和调节机制进行综述。例如,许多引导软骨形成的信号分子,如转化生长因子-β、骨形态发生蛋白、成纤维细胞生长因子和Wnt信号通路,以及转录调节因子,如Sox家族,都已被确定。此外,细胞外基质成分在这一发育过程中也起着重要作用,如胶原蛋白II和多功能蛋白聚糖等蛋白聚糖可促进软骨祖细胞的软骨形成潜能,这一点已得到证实。越来越多关于控制软骨形成的因素的证据以及不同来源祖细胞数量的增加,有望有助于创建组织工程平台,从而克服许多与软骨缺陷相关的发育性或退行性疾病。

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