Zhang Qingyu, Li Junyou, Wang Cheng, Li Zhizhuo, Luo Pan, Gao Fuqiang, Sun Wei
Department of Orthopedics, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan 250021, China.
School of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, South Korea.
Research (Wash D C). 2024 Apr 25;7:0340. doi: 10.34133/research.0340. eCollection 2024.
The methylation of adenosine base at the nitrogen-6 position is referred to as "N6-methyladenosine (mA)" and is one of the most prevalent epigenetic modifications in eukaryotic mRNA and noncoding RNA (ncRNA). Various mA complex components known as "writers," "erasers," and "readers" are involved in the function of mA. Numerous studies have demonstrated that mA plays a crucial role in facilitating communication between different cell types, hence influencing the progression of diverse physiological and pathological phenomena. In recent years, a multitude of functions and molecular pathways linked to mA have been identified in the osteogenic, adipogenic, and chondrogenic differentiation of bone mesenchymal stem cells (BMSCs). Nevertheless, a comprehensive summary of these findings has yet to be provided. In this review, we primarily examined the mA alteration of transcripts associated with transcription factors (TFs), as well as other crucial genes and pathways that are involved in the differentiation of BMSCs. Meanwhile, the mutual interactive network between mA modification, miRNAs, and lncRNAs was intensively elucidated. In the last section, given the beneficial effect of mA modification in osteogenesis and chondrogenesis of BMSCs, we expounded upon the potential utility of mA-related therapeutic interventions in the identification and management of human musculoskeletal disorders manifesting bone and cartilage destruction, such as osteoporosis, osteomyelitis, osteoarthritis, and bone defect.
腺苷碱基在氮-6位置的甲基化被称为“N6-甲基腺苷(mA)”,是真核生物信使核糖核酸(mRNA)和非编码核糖核酸(ncRNA)中最普遍的表观遗传修饰之一。各种被称为“写入器”“擦除器”和“读取器”的mA复合成分参与了mA的功能。大量研究表明,mA在促进不同细胞类型之间的通讯中起着关键作用,从而影响各种生理和病理现象的进展。近年来,在骨间充质干细胞(BMSCs)的成骨、成脂和成软骨分化中,已经发现了许多与mA相关的功能和分子途径。然而,尚未对这些发现进行全面总结。在本综述中,我们主要研究了与转录因子(TFs)相关的转录本的mA改变,以及参与BMSCs分化的其他关键基因和途径。同时,深入阐明了mA修饰、微小核糖核酸(miRNAs)和长链非编码核糖核酸(lncRNAs)之间的相互作用网络。在最后一部分,鉴于mA修饰对BMSCs成骨和成软骨的有益作用,我们阐述了与mA相关的治疗干预措施在识别和管理表现出骨和软骨破坏的人类肌肉骨骼疾病(如骨质疏松症、骨髓炎、骨关节炎和骨缺损)中的潜在效用。