MiR-21——骨再生及多种骨疾病的重要调控因子

MicroRNA-21—an important regulator of bone regeneration and various bone diseases

背景:MiR-21是由初级转录加工而成的非编码RNA,在生长发育、癌症诊治、免疫反应、成骨分化及骨骼再生等生物学功能中发挥着重要作用。目的:综述骨中miR-21的细胞靶点、调控骨再生的分子机制以及miR-21在骨骼疾病中的作用。方法:以“miR-21,bone,osteogenic differentiation,osteoclast differentiation,skeletal muscle,bone regeneration”为英文检索词,以“miR-21,骨,骨骼肌,骨再生”为中文检索词,由第一作者检索2000年至2020年4月PubMed数据库、中国知网、万方全文数据库,查阅与miR-21实验研究相关的文献,最终保留50篇文献进行综述。结果与结论:①近年来,miR-21除了作为癌基因被深入研究外,在骨骼细胞增殖、分化、代谢等方面也受到广泛关注;②具体来说,miR-21能通过调控转化生长因子β诱导基因等基因表达介导骨骼肌的生长发育;miR-21能通过靶向特定的信号通路和相关基因表达促进骨髓间充质干细胞的成骨作用;还能通过c-Fos/抑癌基因程序性死亡因子4调控破骨细胞分化的正反馈,促进RANKL诱导的破骨细胞形成;亦可以调节树突状细胞的分化、间接调控缺氧诱导因子1α和血管内皮生长因子的表达介导干细胞成血管生成;③除此之外,miR-21与骨质疏松、骨肉瘤、多发性骨髓瘤、膝骨关节炎和强直性脊柱炎等骨病变密切相关。

BACKGROUND:As a non-coding RNA processed by primary transcription,microRNA-21(miR-21)plays an important role in biological functions such as growth and development,cancer diagnosis and treatment,immune response,osteogenic differentiation and bone regeneration.OBJECTIVE:To review the cellular targets of miR-21 in bone,the molecular mechanisms that regulate bone regeneration,and the role of miR-21 in bone disease.METHODS:With the keywords of“mir-21,bone,osteogenic differentiation of osteoclast differentiation,skeletal muscle,bone regeneration”in English and“miR-21,bone,skeletal muscle,bone regeneration”in Chinese,PubMed,CNKI,and WanFang databases were retrieved by the first author for articles regarding miR-21 published from 2000 to April 2020.Finally 50 articles were retained for review.RESULTS AND CONCLUSION:In recent years,miR-21 has not only been deeply studied as an oncogene,but also received extensive attention in the proliferation,differentiation,metabolism and other aspects of bone cells.Specifically,miR-21 can mediate the growth and development of skeletal muscle by regulating the expression of transforming growth factorβinduced gene and other genes.MiR-21 can promote the osteogenesis of bone marrow mesenchymal stem cells by targeting specific signaling pathways and related gene expression.It can also regulate the positive feedback of osteoclast differentiation through c-Fos/tumor suppressor gene programmed death factor 4,and promote the formation of osteoclasts induced by RANKL.It also regulates the differentiation of dendritic cells and indirectly regulates the expression of hypoxia inducible factor 1αand vascular endothelial growth,which mediates the angiogenesis of stem cells.In addition,miR-21 is closely associated with osteoporosis,osteosarcoma,multiple myeloma,knee osteoarthritis and ankylosing spondylitis.