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人成纤维细胞作为骨代谢紊乱研究模型

Human Fibroblasts as a Model for the Study of Bone Disorders.

机构信息

Department of Clinical Genetics, Amsterdam Movement Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Department of Clinical Chemistry, Amsterdam Movement Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

出版信息

Front Endocrinol (Lausanne). 2020 Jun 19;11:394. doi: 10.3389/fendo.2020.00394. eCollection 2020.

Abstract

Bone tissue degeneration is an urgent clinical issue, making it a subject of intensive research. Chronic skeletal disease forms can be prevalent, such as the age-related osteoporosis, or rare, in the form of monogenetic bone disorders. A barrier in the understanding of the underlying pathological process is the lack of accessibility to relevant material. For this reason, cells of non-bone tissue are emerging as a suitable alternative for models of bone biology. Fibroblasts are highly suitable for this application; they populate accessible anatomical locations, such as the skin tissue. Reports suggesting their utility in preclinical models for the study of skeletal diseases are increasingly becoming available. The majority of these are based on the generation of an intermediate stem cell type, the induced pluripotent stem cells, which are subsequently directed to the osteogenic cell lineage. This intermediate stage is circumvented in transdifferentiation, the process regulating the direct conversion of fibroblasts to osteogenic cells, which is currently not well-explored. With this mini review, we aimed to give an overview of existing osteogenic transdifferentiation models and to inform about their applications in bone biology models.

摘要

骨组织退化是一个紧迫的临床问题,因此成为了密集研究的课题。慢性骨骼疾病形式可能很普遍,如与年龄相关的骨质疏松症,或者很少见,以单基因骨骼疾病的形式出现。理解潜在病理过程的一个障碍是缺乏相关材料的可及性。出于这个原因,非骨骼组织的细胞正在成为骨骼生物学模型的合适替代品。成纤维细胞非常适合这种应用;它们存在于可及的解剖位置,如皮肤组织。越来越多的报告表明它们在骨骼疾病的临床前模型中的应用具有实用性。这些报告中的大多数都是基于生成一种中间干细胞类型,即诱导多能干细胞,然后将其定向到成骨细胞谱系。在转分化中可以绕过这个中间阶段,转分化是调节成纤维细胞向成骨细胞直接转化的过程,目前对此研究还不充分。通过这篇小型综述,我们旨在概述现有的成骨细胞转分化模型,并介绍它们在骨骼生物学模型中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edca/7318867/9bba92d77485/fendo-11-00394-g0001.jpg

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