Yalaev B I, Khusainova R I
Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Center of the Russian Academy of Sciences, Ufa, Russia Saint Petersburg State University, St. Petersburg, Russia.
Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Center of the Russian Academy of Sciences, Ufa, Russia Saint Petersburg State University, St. Petersburg, Russia Ufa University of Science and Technology, Ufa, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2023 Jul;27(4):401-410. doi: 10.18699/VJGB-23-48.
Discovery of molecular mechanisms of primary osteoporosis development is fundamental to understand the pathogenesis of musculoskeletal diseases in general and for identifying key links in the genetic and epigenetic regulation of bone remodelling genes. The number of identified molecular genetic markers for osteoporosis is increasing but there is a need to describe their functional interactions. These interactions have been determined to be associated with the control of expression of a number of transcription factors and the differentiation of mesenchymal stem cells through the pathway of osteoblastogenesis or adipogenesis, and monocytic precursors through the pathway of osteoclastogenesis. The results of epigenetic studies have significantly increased the understanding of the role of post-translational modifications of histones, DNA methylation and RNA interference in the osteoporosis pathogenesis and in bone remodelling. However, the knowledge should be systematised and generalised according to the results of research on the role of epigenetic modifiers in the development of osteoporosis, and the influence of each epigenetic mechanism on the individual links of bone remodelling during ontogenesis of humans in general, including the elderly, should be described. Understanding which mechanisms and systems are involved in the development of this nosology is of interest for the development of targeted therapies, as the possibility of using microRNAs to regulate genes is now being considered. Systematisation of these data is important to investigate the differences in epigenetic marker arrays by race and ethnicity. The review article analyses references to relevant reviews and original articles, classifies information on current advances in the study of epigenetic mechanisms in osteoporosis and reviews the results of studies of epigenetic mechanisms on individual links of bone remodelling.
发现原发性骨质疏松症发展的分子机制对于理解一般肌肉骨骼疾病的发病机制以及确定骨重塑基因的遗传和表观遗传调控中的关键环节至关重要。已鉴定出的骨质疏松症分子遗传标记数量在不断增加，但需要描述它们的功能相互作用。这些相互作用已被确定与多种转录因子的表达控制以及间充质干细胞通过成骨细胞生成途径或脂肪生成途径的分化，以及单核细胞前体通过破骨细胞生成途径的分化有关。表观遗传学研究结果显著增进了对组蛋白翻译后修饰、DNA甲基化和RNA干扰在骨质疏松症发病机制及骨重塑中的作用的理解。然而，应根据关于表观遗传修饰剂在骨质疏松症发展中的作用的研究结果进行系统化和概括，并应描述每种表观遗传机制对一般人类个体发育过程中骨重塑各个环节的影响，包括老年人。了解哪些机制和系统参与了这种疾病的发展对于靶向治疗的开发很有意义，因为现在正在考虑使用微小RNA来调节基因的可能性。对这些数据进行系统化对于按种族和民族研究表观遗传标记阵列的差异很重要。这篇综述文章分析了相关综述和原始文章的参考文献，对骨质疏松症表观遗传机制研究的当前进展信息进行了分类，并综述了表观遗传机制在骨重塑各个环节的研究结果。
