Fiani Brian, Covarrubias Claudia, Jarrah Ryan
Neurosurgery, Desert Regional Medical Center, Palm Springs, USA.
Medicine, Universidad Anahuac Queretaro, Santiago de Querétaro, MEX.
Cureus. 2021 May 22;13(5):e15182. doi: 10.7759/cureus.15182.
Intervertebral disc (IVD) degeneration is a progressive and painful pathology that can root from mechanical, biochemical, and environmental stressors. However, recent advancements in biogenetics have now found a predominating genetic influence. Nevertheless, despite these advancements, the pathophysiology of IVD degeneration remains poorly understood. In the first of our two-part series, we will characterize some of the most recent and best-studied genes in the context of intervertebral disc degeneration. We will attempt to formulate the first contemporary gene guide that characterizes the genetic profile of IVD degeneration. The genes of interest include aggrecan (ACAN), matrix metalloproteinase 2 (MMP2), vitamin D receptor (VDR), interleukin 1 alpha (IL1A), and those encoded for collagens such as collagen type XI alpha 1 chain (COL11A1), collagen type I alpha 1 chain (COL1A1), collagen type IX alpha 2 chain (COL9A2), and collagen type IX alpha 3 chain (COL9A3). Genetic analysis studies reveal that these genes play vital roles in maintaining the structural integrity of the intervertebral disc, activating enzymes involved in the extracellular matrix, and promoting connective tissue formation. Nevertheless, characterizing these genes alone is not enough to understand the pathophysiology of IVD degeneration. Therefore, further studies are warranted to understand molecular signalling pathways of IVD degeneration better and ultimately create more sophisticated genetic and cell-based therapies to improve patient outcomes.
椎间盘退变是一种渐进性的疼痛性病理状况,其根源可能是机械、生化和环境应激因素。然而,生物遗传学的最新进展现已发现了主要的遗传影响。尽管如此,尽管有这些进展,椎间盘退变的病理生理学仍知之甚少。在我们这个两部分系列文章的第一篇中,我们将在椎间盘退变的背景下描述一些最近研究最多且最深入的基因。我们将尝试制定第一份当代基因指南,以描述椎间盘退变的基因特征。感兴趣的基因包括聚集蛋白聚糖(ACAN)、基质金属蛋白酶2(MMP2)、维生素D受体(VDR)、白细胞介素1α(IL1A),以及那些编码胶原蛋白的基因,如XI型胶原蛋白α1链(COL11A1)、I型胶原蛋白α1链(COL1A1)、IX型胶原蛋白α2链(COL9A2)和IX型胶原蛋白α3链(COL9A3)。基因分析研究表明,这些基因在维持椎间盘的结构完整性、激活参与细胞外基质的酶以及促进结缔组织形成方面发挥着至关重要的作用。然而,仅对这些基因进行表征还不足以理解椎间盘退变的病理生理学。因此,有必要进行进一步的研究,以更好地了解椎间盘退变的分子信号通路,并最终创造出更复杂的基于基因和细胞的疗法,以改善患者的治疗效果。