Abstract:
MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3\'-untranslated regions (3\'-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/β-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-βs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-β/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science.
摘要:
microRNAs(miRNAs)是一个小家族,单股,和长度约19至22个核苷酸的非蛋白质编码RNA,据报道,在控制骨骼发育中具有重要作用。miRNAs通过谱系定型和成熟阶段对成骨细胞分化有很大影响,以及通过控制成骨信号转导通路的活性。一般来说,miRNA可以调节细胞的干性,扩散,分化,通过结合靶基因的3'-非翻译区(3'-UTR)和凋亡,然后可以随后经历信使RNA(mRNA)降解或蛋白质翻译抑制。MiRNAs通过调节多个信号级联和必需转录因子来管理成骨分化中的基因表达,包括转化生长因子-β(TGF-β)/骨形态发生蛋白(BMP),无翼/Int-1(Wnt)/β-catenin,缺口,和Hedgehog信号通路;Runt相关转录因子2(RUNX2);和osterix(Osx)。这表明miRNA在调节多种成骨细胞功能中是必需的。TGF-βs和BMPs转导信号并在成骨细胞生成中发挥不同的功能,骨骼发育和骨形成,骨稳态,和疾病。在这里,我们强调了描述miRNA对经典TGF-β/BMP信号传导的体外和体内研究的现状,它们对成骨细胞的影响,并了解它们对开发可能的治疗方法的作用机制。在这次审查中,特别关注和全面的数据库搜索集中在2000年至2022年之间发表的相关作品,使用PubMed的资源,谷歌学者,Scopus,和WebofScience。