Li Zehui, Meng Keyu, Lan Shanwei, Ren Zhengda, Lai Zhongming, Ao Xiang, Liu Zhongyuan, Xu Jiajia, Mo Xiaoyi, Zhang Zhongmin
Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
Int J Biol Sci. 2025 Jan 13;21(3):1065-1080. doi: 10.7150/ijbs.104460. eCollection 2025.
As a type of epigenetic modifications, mRNA modifications regulate the metabolism of mRNAs, thereby influencing gene expression. Previous studies have indicated that dysregulation of mRNA modifications is closely associated with the occurrence and progression of bone diseases (BDs). In this study, we first introduced the dynamic regulatory processes of five major mRNA modifications and their effects on the nucleus export, stability, and translation of mRNAs. We then summarized the mechanisms of mRNA modifications involved in the development of osteoporosis, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, fractures, osteomyelitis, and osteosarcoma. Finally, we reviewed therapeutic strategies for BDs based on the above mechanisms, focusing on regulating osteoblast and osteoclast differentiation, inhibiting cellular senescence and injury, and alleviating inflammation. This review identified mRNA modifications as potential targets for treating BDs and proposes perspectives on the diversity, targetability, and safety of mRNA-modifying therapies.
作为一种表观遗传修饰，mRNA修饰调节mRNA的代谢，从而影响基因表达。先前的研究表明，mRNA修饰的失调与骨疾病（BDs）的发生和发展密切相关。在本研究中，我们首先介绍了五种主要mRNA修饰的动态调节过程及其对mRNA核输出、稳定性和翻译的影响。然后，我们总结了mRNA修饰参与骨质疏松症、骨关节炎、类风湿性关节炎、强直性脊柱炎、骨折、骨髓炎和骨肉瘤发生发展的机制。最后，我们基于上述机制综述了BDs的治疗策略，重点关注调节成骨细胞和破骨细胞分化、抑制细胞衰老和损伤以及减轻炎症。本综述确定mRNA修饰为治疗BDs的潜在靶点，并对mRNA修饰疗法的多样性、靶向性和安全性提出了展望。
