微小RNA调控组蛋白去乙酰化酶治疗骨相关疾病的发展现状

MicroRNA regulates histone deacetylase in the treatment of bone-related diseases

背景:组蛋白去乙酰化酶的表观遗传在骨相关疾病中起着关键作用,近年来研究发现miRNA作为一种新的治疗抑制剂,能与不同种类的组蛋白去乙酰化酶靶向结合影响其表达,进而影响骨相关疾病的发生发展。目的:综述miRNA特异性调控不同类型组蛋白去乙酰酶治疗各种骨相关疾病的治疗进展,为以后临床治疗骨相关疾病提供新的治疗方向。方法:检索PubMed数据库、万方数据库、CNKI中国期刊全文数据库、Elsevier数据库以及中国生物医学文献数据库2000至2020年收录的相关文献。英文检索词为"HDAC,miRNA,bone,mesenchymal stem cells,osteoclast,chondrocyte,osteoarthrosis,osteosarcoma",中文检索词为"组蛋白去乙酰化酶,微小RNA,骨,间充质干细胞,破骨细胞,软骨细胞,骨关节炎,骨肉瘤",最终纳入79篇文献进行归纳总结。结果与结论:①研究发现组蛋白去乙酰化酶通过调控间充质干细胞成骨成脂分化、破骨细胞增殖与活力、骨肉瘤细胞侵袭与转移影响骨相关疾病如骨质疏松症、骨关节炎和骨肉瘤等的发生发展;②miRNA是一类参与基因转录后负向调节的内源性非编码RNA,研究报道miRNA能针对骨骼中的组蛋白去乙酰化酶进行调控,影响骨相关疾病发展。

BACKGROUND:Histone deacetylases play a key role in bone diseases through epigenetic regulation.Recent studies have found that microRNA(miRNA),as a new treatment inhibitor, can bind with different types of histone deacetylases to affect its expression, thus influencing the occurrence and development ofbone-related diseases.OBJECTIVE: To review the effects of various miRNAs targeting different types of histone deacetylases on bone diseases, and provide a new therapeutic directionfor the clinical treatment of bone diseases.METHODS: We searched PubMed, WanFang, CNKI, Elsevier and Chinese Biomedical Literature Database for relevant literature published from 2000 to 2020.The search terms were “HDAC, miRNA;bone, mesenchymal stem cells, osteoclast, chondrocyte, osteoarthrosis, osteosarcoma” in Chinese and English,respectively. Finally, 79 articles were included for review.RESULTS AND CONCLUSION: Histone deacetylases can affect the occurrence and progression of bone diseases such as osteoporosis, osteoarthritis andosteosarcoma by regulating the osteoblastic and adipogenic differentiation of mesenchymal stem cells, osteoclast proliferation and viability, as well asosteosarcoma cell invasion and metastasis. MiRNA is a type of endogenous non-coding RNA involved in post-transcriptional negative feedback regulation.Studies have reported that miRNA can regulate the expression of histone deacetylases in the bones and affect the development of bone diseases.