N6- 甲基腺苷甲基转移酶样 3 调控骨代谢及其相关疾病的作用.

BACKGROUND: As one of the most prevalent types of RNA modification, N6-methyladenosine (m6A) methylation has emerged as a bright spot for regulating various diseases by interfering with RNA splicing, translation, nuclear export and decay. However, studies of methyltransferase-like 3 (METTL3)-mediated epigenetic modification of m6A methylation on bone metabolism have not been summarized. OBJECTIVE: To summarize the potential molecular mechanism of m6 A core methyltransferase METTL3 in bone metabolism and its latest progress and future prospects in regulating osteogenic differentiation, osteoclastic differentiation, cartilage apoptosis, extracellular matrix degeneration, and bone metabolismrelated diseases, thereby offering new insights into the study of the pathological mechanism of bone metabolism-related diseases and then providing a theoretical reference for the early diagnosis, clinical treatment, and prognosis of the diseases. METHODS: The CNKI database was searched with the Chinese keywords of “N6-methyladenine, methyltransferase-like 3, osteoblasts, osteoclasts, chondrocytes, mesenchymal stem cells, bone metabolism, osteoporosis, osteoarthritis, orthopedic diseases, treatment.” The PubMed database was searched with the English keywords of “m6A, METTL3, Osteoblast, osteoclasts, chondrocyte, mesenchymal stem cells, bone metabolism, osteoporosis, osteoarthritis, orthopedic disease, therapy.” Literature on METTL3/m6A-mediated RNA methylation in orthopedic diseases was retrieved from database establishment to March 2022. As per the inclusion and exclusion criteria, 35 articles were finally selected for review. RESULTS AND CONCLUSION: The role of METTL3 in osteogenesis is controversial and remains to be further studied in depth. METTL3/m6A-mediated RNA methylation can regulate osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells through a variety of mechanisms, but the specific mechanism is not clear. METT3 regulation of osteoclast differentiation function is essential for maintaining bone homeostasis as well as maintaining bone integrity. METTL3 plays an important role in the development of bone metabolism-related diseases; therefore, METTL3 overexpression may become a new alternative therapy for the treatment of human bone metabolism-related diseases such as osteoporosis. [ABSTRACT FROM AUTHOR]