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骨生成的表观遗传调控:促进骨再生的途径

Epigenetic Control of Osteogenesis: Pathways Toward Improved Bone Regeneration.

作者信息

Stetsiv Marta, Abdulsalam Sakinah, Dauphinee Drew, Sanjay Archana, Guzzo Rosa M

机构信息

Department of Orthopaedic Surgery, School of Medicine, UConn Health, 263 Farmington Avenue, Farmington, CT, 06030, USA.

Department of Neuroscience, School of Medicine, UConn Health, 263 Farmington Avenue, Farmington, CT, 06030, USA.

出版信息

Curr Osteoporos Rep. 2025 Jun 18;23(1):27. doi: 10.1007/s11914-025-00923-4.

Abstract

PURPOSE OF REVIEW

In this review, we summarize our evolving understanding of the epigenetic mechanisms directing the osteogenic differentiation of skeletal progenitor cells.

RECENT FINDINGS

Advances in genome-wide approaches used to profile chromatin accessibility and histone modifications in skeletal progenitors have uncovered chromatin remodeling associated with progression of osteoblast differentiation and the key regulatory nodes driving this process. Utilization of cell culture systems and genetic mouse models highlight the key enzymes regulating histone posttranslational modifications and DNA methylation that promote the transition of cells from progenitor to mature osteoblast stage. Herein, the described studies provide emerging insights gained from pharmacologic targeting of chromatin modifiers promoting osteogenic differentiation of skeletal progenitors. While our fundamental understanding of chromatin modifiers and factors regulating chromatin accessibility and transcriptional activity in skeletal progenitors continues to develop, future research may inform new therapeutic approaches to promote osteoblast differentiation and enhance mineralization to augment fracture repair.

摘要

综述目的

在本综述中,我们总结了对指导骨骼祖细胞成骨分化的表观遗传机制不断演变的理解。

最新发现

用于分析骨骼祖细胞染色质可及性和组蛋白修饰的全基因组方法的进展,揭示了与成骨细胞分化进程相关的染色质重塑以及驱动这一过程的关键调控节点。细胞培养系统和基因小鼠模型的应用突出了调节组蛋白翻译后修饰和DNA甲基化的关键酶,这些酶促进细胞从祖细胞向成熟成骨细胞阶段的转变。在此,所描述的研究提供了从促进骨骼祖细胞成骨分化的染色质修饰剂的药理学靶向中获得的新见解。虽然我们对骨骼祖细胞中染色质修饰剂以及调节染色质可及性和转录活性的因子的基本理解仍在不断发展,但未来的研究可能会为促进成骨细胞分化和增强矿化以促进骨折修复的新治疗方法提供依据。

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