Peking University Third Hospital, Department of Orthopaedics, Beijing, China; Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China; Beijing Key Laboratory of Spinal Disease Research, Beijing, China.
Peking University Third Hospital, Department of Orthopaedics, Beijing, China; Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China; Beijing Key Laboratory of Spinal Disease Research, Beijing, China.
Ageing Res Rev. 2022 May;77:101598. doi: 10.1016/j.arr.2022.101598. Epub 2022 Feb 24.
Spinal stenosis is a common degenerative spine disorder in the aged population and the spinal ligament aging is a main contributor to this chronic disease. However, the underlying mechanisms of spinal ligament aging remain unclear. Epigenetics is the study of heritable and reversible changes in the function of a gene or genome that occur without any alteration in the primary DNA sequence. Epigenetic alterations have been demonstrated to play crucial roles in age-related diseases and conditions, and they are recently studied as biomarkers and therapeutic targets in the field of cancer research. The main epigenetic modifications, including DNA methylation alteration, histone modifications as well as dysregulated noncoding RNA modulation, have all been implicated in spinal ligament aging diseases. DNA methylation modulates the expression of critical genes including WNT5A, GDNF, ACSM5, miR-497 and miR-195 during spinal ligament degeneration. Histone modifications widely affect gene expression and obvious histone modification abnormalities have been found in spinal ligament aging. MicroRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) exert crucial regulating effects on spinal ligament aging conditions via targeting various osteogenic or fibrogenic differentiation related genes. To our knowledge, there is no systematic review yet to summarize the involvement of epigenetic mechanisms of spinal ligament aging in degenerative spinal diseases. In this study, we systematically discussed the different epigenetic modifications and their potential functions in spinal ligament aging process.
脊柱狭窄症是一种常见的老年人群退行性脊柱疾病，脊柱韧带老化是这种慢性疾病的主要原因。然而，脊柱韧带老化的潜在机制尚不清楚。表观遗传学是研究基因或基因组功能的可遗传和可逆变化的学科，这些变化发生在不改变原始 DNA 序列的情况下。表观遗传改变已被证明在与年龄相关的疾病和病症中发挥关键作用，并且它们最近作为癌症研究领域的生物标志物和治疗靶点进行了研究。主要的表观遗传修饰，包括 DNA 甲基化改变、组蛋白修饰以及失调的非编码 RNA 调节，都与脊柱韧带老化疾病有关。DNA 甲基化调节包括 WNT5A、GDNF、ACSM5、miR-497 和 miR-195 等关键基因的表达，这些基因在脊柱韧带退化过程中。组蛋白修饰广泛影响基因表达，在脊柱韧带老化中发现了明显的组蛋白修饰异常。微小 RNA（miRNA）、长链非编码 RNA（lncRNA）和环状 RNA（circRNA）通过靶向各种成骨或成纤维分化相关基因，对脊柱韧带老化条件发挥关键调节作用。据我们所知，目前还没有系统的综述来总结表观遗传机制在退行性脊柱疾病中对脊柱韧带老化的参与。在这项研究中，我们系统地讨论了不同的表观遗传修饰及其在脊柱韧带老化过程中的潜在功能。
