表观遗传调控在脊柱韧带骨化中的作用研究进展

Research progress of epigenetic regulation in the ossification of spinal ligaments

脊柱韧带骨化以脊柱韧带组织内出现病理性骨组织为特征,好发于颈段和胸段,是造成椎管狭窄的重要病因。骨化块对脊髓或神经根的压迫可导致严重的神经功能障碍,给患者生活质量带来巨大影响。目前脊柱韧带骨化的具体病因及发病机制尚不明确。表观遗传调控在生物体内广泛存在,指在不改变基因组DNA序列的前提下使生物体出现具有可遗传的基因表达改变。作为调控生物多样性的重要形式,表观遗传调控已被证明在多种疾病的发生、发展中扮演重要角色。表观遗传调控有多种表现形式,目前已经发现DNA甲基化、组蛋白修饰和非编码RNA调控在脊柱韧带骨化中发挥作用。基因芯片等测序手段发现骨化与正常脊柱韧带的DNA甲基化谱与非编码RNA的表达都存在显著差异,这些差异可通过直接或间接的途径造成成骨相关靶基因的异常表达,进而影响脊柱韧带的骨化进程。此外,这些表观遗传调控机制之间存在交互作用,构成一个庞大且复杂的调控网络。因此,深入了解不同表观遗传调控机制及其之间的联系在脊柱韧带骨化的起始与进展阶段所起的作用,有望为脊柱韧带骨化相关性疾病的临床诊断与治疗提供有价值的参考。

Ossification of the spinal ligaments(OSL)is characterized by the appearance of pathologic bone tissue within the spinal ligamentous tissue.OSL tends to occur in the cervical and thoracic segments with important cause of spinal stenosis.Compression of the spinal cord or nerve roots by ossified masses can lead to severe neurological dysfunction,which has a tremendous impact on the quality of life of patients.However,the exact etiology and pathogenesis of OSL are still unclear.Epigenetic regulation is widespread in organisms and refers to the appearance of heritable changes in gene expression without alteration in genomic DNA sequence.As an important form of biodiversity regulation,epigenetic regulation plays an important role in development of several diseases.Epigenetic regulation has multiple manifestations in OSL,including DNA methylation,histone modifications,and non-coding RNA regulation.Sequencing tools,such as gene microarrays,have revealed significant differences in DNA methylation profiles and non-coding RNA expression between ossified and normal spinal ligaments.These differences can cause abnormal expression of osteogenesis-related target genes through direct or indirect pathways,thus affecting the ossification process of spinal ligaments.In addition,interactions between these epigenetic regulatory mechanisms constitute a large and complex regulatory network.Consequently,an in-depth understanding of the role of different epigenetic regulatory mechanisms and the linkages between them in the initiation and progression stages of OSL is expected to provide a valuable reference for the clinical diagnosis and treatment of OSL-related diseases.