Thus far, there are more than known 150 modifications to RNA, in which common internal modifications of mRNA include N6-methyladenosine (m6A), N1-methyladenosine, and 5-methylcytosine. Among them, m6A RNA modification is one of the highest abundance modifications in eukaryotes, regulating mechanisms controlling gene expression at the post-transcription level. As an invertible and dynamic epigenetic marker, m6A base modification influences almost all vital biological processes, cellular components, and molecular functions. Once the m6A modification process is abnormal, a series of diseases—including cancer, neurological diseases, and growth disorders—will be caused. Besides, several base modification activities also have been created by noncoding RNAs (ncRNAs), for instance, microRNAs, and circular RNAs, long ncRNAs, which were dynamically regulated during bone and cartilage pathophysiology processes. Therefore, it has now been clear that dynamic modification on coding RNAs and ncRNAs represents a completely new way to modulate genetic information. In this review, we highlight up-to-date progress and applications of m6A RNA modification in bone and cartilage pathophysiology, and we discuss the pathological roles and underlying molecular mechanism of m6A modifications in osteoarthritis and osteoporosis and osteosarcoma pathogenesis.

中文翻译：

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对 N6-甲基腺苷 RNA 修饰在骨病理生理学中的作用的新见解

迄今为止，已知的 RNA 修饰超过 150 种，其中常见的 mRNA 内部修饰包括 N6-甲基腺苷 (m6A)、N1-甲基腺苷和 5-甲基胞嘧啶。其中，m6A RNA修饰是真核生物中丰度最高的修饰之一，在转录后水平调控基因表达的调控机制。作为一种可逆的动态表观遗传标记，m6A 碱基修饰影响几乎所有重要的生物过程、细胞成分和分子功能。一旦m6A修饰过程异常，就会引发一系列疾病——包括癌症、神经系统疾病和生长障碍。此外，非编码 RNA (ncRNA) 也产生了几种碱基修饰活动，例如 microRNA、环状 RNA、长 ncRNA、其在骨和软骨病理生理过程中受到动态调节。因此，现在已经清楚，对编码 RNA 和 ncRNA 的动态修饰代表了一种全新的调节遗传信息的方式。在这篇综述中，我们重点介绍了 m6A RNA 修饰在骨和软骨病理生理学中的最新进展和应用，并讨论了 m6A 修饰在骨关节炎、骨质疏松症和骨肉瘤发病机制中的病理作用和潜在分子机制。