Department of Orthodontics, Texas A&M University College of Dentistry, 3302 Gaston ave, Dallas, TX, 75246, USA.
Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, USA.
Curr Osteoporos Rep. 2020 Jun;18(3):199-209. doi: 10.1007/s11914-020-00586-3.
The goal of this review is to obtain a better understanding of how chondrogenesis defines skeletal development via cell transdifferentiation from chondrocytes to bone cells.
A breakthrough in cell lineage tracing allows bone biologists to trace the cell fate and demonstrate that hypertrophic chondrocytes can directly transdifferentiate into bone cells during endochondral bone formation. However, there is a knowledge gap for the biological significance of this lineage extension and the mechanisms controlling this process. This review first introduces the history of the debate on the cell fate of chondrocytes in endochondral bone formation; then summarizes key findings obtained in recent years, which strongly support a new theory: the direct cell transdifferentiation from chondrocytes to bone cells precisely connects chondrogenesis (for providing a template of the future skeleton, classified as phase I) and osteogenesis (for finishing skeletal construction, or phase II) in a continuous lineage-linked process of endochondral bone formation and limb elongation; and finally outlines nutrition factors and molecules that regulate the cell transdifferentiation process during the relay from chondrogenesis to osteogenesis.
本文旨在深入了解软骨细胞的细胞转分化在骨骼发育中的作用,即软骨细胞如何向成骨细胞分化来定义骨骼发育。
细胞谱系示踪技术的突破使骨生物学家能够追踪细胞命运,并证明肥大软骨细胞可以在软骨内骨形成过程中直接向成骨细胞转分化。然而,对于这种谱系延伸的生物学意义以及控制该过程的机制,目前仍存在知识空白。本综述首先介绍了软骨细胞在软骨内骨形成中细胞命运争论的历史;然后总结了近年来获得的关键发现,这些发现强烈支持了一个新理论:软骨细胞向成骨细胞的直接细胞转分化,精确地将软骨生成(为未来骨骼提供模板,归为 I 期)和骨生成(完成骨骼构建,或 II 期)在软骨内骨形成和肢体延长的连续谱系相关过程中连接起来;最后概述了营养因子和分子在从软骨生成到骨生成的接力过程中调节细胞转分化的过程。