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隋昊, 张陶. 组蛋白去甲基化酶在间充质干细胞成骨和成软骨分化中的作用综述[J]. 四川大学学报(医学版), 2021, 52(3): 364-372. DOI: 10.12182/20210560202
引用本文: 隋昊, 张陶. 组蛋白去甲基化酶在间充质干细胞成骨和成软骨分化中的作用综述[J]. 四川大学学报(医学版), 2021, 52(3): 364-372. DOI: 10.12182/20210560202
SUI Hao, ZHANG Tao. The Role of Histone Demethylase in Osteogenic and Chondrogenic Differentiation of Mesenchymal Stem Cells: A Literature Review[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(3): 364-372. DOI: 10.12182/20210560202
Citation: SUI Hao, ZHANG Tao. The Role of Histone Demethylase in Osteogenic and Chondrogenic Differentiation of Mesenchymal Stem Cells: A Literature Review[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(3): 364-372. DOI: 10.12182/20210560202

组蛋白去甲基化酶在间充质干细胞成骨和成软骨分化中的作用综述

The Role of Histone Demethylase in Osteogenic and Chondrogenic Differentiation of Mesenchymal Stem Cells: A Literature Review

  • 摘要: 间充质干细胞(MSCs)的增殖和多向分化潜能使其广泛用于骨、软骨修复新疗法的开发,虽然已初步探明MSCs成骨、成软骨分化的基因表达谱,但启动MSCs分化的关键因子仍不明确,限制了其在骨、软骨组织工程中的应用。组蛋白去甲基化酶(KDMs)介导的表观遗传机制是调控MSCs谱系分化的关键环节。含Tower结构域的赖氨酸特异性组蛋白去甲基化酶家族(LSD)及含Jumonji C(JmjC)结构域的组蛋白去甲基化酶家族通过调控Runt相关转录因子2(RUNX2)、成骨相关转录因子抗体(OSX)、骨钙素(OCN)在内的多种成骨相关基因的表达以介导MSCs成骨向分化。KDM2/4/6亚家族等通过以SRY-related high-mobility-group-box gene 9(SOX9)为中心的多条通路调控MSCs成软骨分化。此外,纳米拓扑结构、mircoRNAs等通过上、下调KDMs调控多种成骨和成软骨转录因子的表达。本文对KDMs在MSCs成骨和成软骨分化中的作用进行综述,以帮助读者更好地理解骨、软骨损伤疾病的发病机制,促进为骨、软骨组织工程未来的临床应用。

     

    Abstract: The proliferation and multi-directional differentiation potential of mesenchymal stem cells (MSCs) enabled its wide use in the development of new therapies for bone and cartilage repair. Although preliminary work has been done to verify the gene expression profile of MSCs osteogenic and chondrogenic differentiation, it is still unclear what key factors initiate the differentiation of MSCs, resulting in its limited application in bone and cartilage tissue engineering. The epigenetic mechanism mediated by histone demethylases (lysine K-specific histone demethylases, KDMs) is the key link in regulating MSCs lineage differentiation. The lysine-specific histone demethylase (LSD) family containing Tower domain and the histone demethylase family containing Jumonji C (JmjC) domain regulate the expression of various osteogenic-related genes, including Runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN), to mediate MSCs osteogenic differentiation. The KDM2/4/6 subfamilies regulate the chondrogenic differentiation of MSCs through multiple pathways centered on SRY-related high-mobility-group-box gene 9 (SOX9). In addition, nanotopology, mircoRNAs, etc. regulate the expression of a variety of osteogenic and chondrogenic transcription factors through up- and down-regulation of KDMs. In summary, the role of histone demethylase in the osteogenic and chondrogenic differentiation of mesenchymal stem cells will help us better understand the pathogenesis of bone and cartilage damage diseases, and establish the foundation of future clinical applications for bone and cartilage tissue engineering.

     

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