Transcriptional control of chondrocyte specification and differentiation.
Transcriptional control of chondrocyte specification and differentiation.
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DOI：
10.1016/j.semcdb.2016.10.004
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发表时间：
2017-02
影响因子：
7.3
通讯作者：
Lefebvre V
中科院分区：
文献类型：
--
作者：
Liu CF;Samsa WE;Zhou G;Lefebvre V
脊椎动物进化出现的一个里程碑是软骨的发明，软骨是一种在建模、保护和补充骨骼方面发挥关键作用的组织。软骨是由软骨细胞形成和维持的。这些细胞来源于多能骨骼祖细胞，它们在经历连续的谱系承诺和分化步骤时执行高度专门化的功能。它们形成软骨原基，这是胚胎的主要骨架。然后，他们将这些原基转化为软骨生长板、骨骼伸长和软骨内成骨的暂时驱动力，或者转化为永久性组织，即关节软骨。软骨细胞的命运决定和分化活动受众多外在和内在信号的控制，它们是由转录因子在基因表达水平上实现的。后者是本次审查的重点。在过去的二十年里，许多研究小组的卓有成效的努力已经导致了数十个关键的软骨形成转录因子的鉴定。这些调控因子属于所有类型的转录因子家族。有些人在一个或几个差异化步骤中扮演着主要角色。他们包括SOX9和RUNX2/3。其他人会果断地协助或对抗这些大师的活动。它们包括Twist1、SOX5/6和MEF2C/D。更多的基因具有组织构图作用，调节细胞存活、增殖和细胞分化的速度。它们包括但不限于含有同源结构域的蛋白质和生长因子信号媒介。我们在这里回顾所有这些因素的当前知识，一次一个超类、一个类和一个家庭。然后，我们将所有知识汇编成转录网络。我们还确定了知识中的剩余差距和未来研究的方向，以填补这些差距，从而为软骨疾病的机制和治疗方案提供新的见解。
A milestone in the evolutionary emergence of vertebrates was the invention of cartilage, a tissue that has key roles in modeling, protecting and complementing the bony skeleton. Cartilage is elaborated and maintained by chondrocytes. These cells derive from multipotent skeletal progenitors and they perform highly specialized functions as they proceed through sequential lineage commitment and differentiation steps. They form cartilage primordia, the primary skeleton of the embryo. They then transform these primordia either into cartilage growth plates, temporary drivers of skeletal elongation and endochondral ossification, or into permanent tissues, namely articular cartilage. Chondrocyte fate decisions and differentiated activities are controlled by numerous extrinsic and intrinsic cues, and they are implemented at the gene expression level by transcription factors. The latter are the focus of this review. Meritorious efforts from many research groups have led over the last two decades to the identification of dozens of key chondrogenic transcription factors. These regulators belong to all types of transcription factor families. Some have master roles at one or several differentiation steps. They include SOX9 and RUNX2/3. Others decisively assist or antagonize the activities of these masters. They include TWIST1, SOX5/6, and MEF2C/D. Many more have tissue-patterning roles and regulate cell survival, proliferation and the pace of cell differentiation. They include, but are not limited to, homeodomain-containing proteins and growth factor signaling mediators. We here review current knowledge of all these factors, one superclass, class, and family at a time. We then compile all knowledge into transcriptional networks. We also identify remaining gaps in knowledge and directions for future research to fill these gaps and thereby provide novel insights into cartilage disease mechanisms and treatment options.