Cauble Meagan A, Mancini Nickolas S, Kalinowski Judith, Lykotrafitis George, Moss Isaac L
UConn Health Department of Orthopaedic Surgery Musculoskeletal Institute Farmington Connecticut USA.
Department of Mechanical Engineering University of Connecticut Storrs Connecticut USA.
JOR Spine. 2020 Sep 23;3(3):e1125. doi: 10.1002/jsp2.1125. eCollection 2020 Sep.
Degeneration of the intervertebral disc (IVD) is a condition that is often associated with debilitating back pain. There are no disease-modifying treatments available to halt the progression of this ubiquitous disorder. This is partly due to a lack of understanding of extracellular matrix (ECM) changes that occur at the micro- and nanometer size scales as the disease progresses. Over the past decade, atomic force microscopy (AFM) has been utilized as a tool to investigate the impact of disease on nanoscale structure of ECM in bone, skin, tendon, and dentin. We have expanded this methodology to include the IVD and report the first quantitative analysis of ECM structure at submicron size scales in a murine model for progressive IVD degeneration. Collagen D-spacing, a metric of nanoscale structure at the fibril level, was observed as a distribution of values with an overall average value of 62.5 ± 2.5 nm. In degenerative discs, the fibril D-spacing distribution shifted towards higher values in both the annulus fibrosus and nucleus pulposus (NP) ( < .05). A novel microstructural feature, , defined by a topographical pit enclosed by fibril-forming matrix was observed in the NP. With degeneration, these microstructures became more numerous and the morphology was altered from circular (aspect ratio 1.0 ± 0.1) to oval (aspect ratio 1.5 ± 0.4), < .005. These analyses provide ECM structural details of the IVD at size scales that have historically been missing in studies of disc degeneration. Knowledge gained from these insights may aid the development of novel disease-modifying therapeutics.
椎间盘退变是一种常与使人衰弱的背痛相关的病症。目前尚无能够阻止这种普遍存在的疾病进展的疾病修饰治疗方法。部分原因是随着疾病进展，对于在微米和纳米尺度上发生的细胞外基质（ECM）变化缺乏了解。在过去十年中，原子力显微镜（AFM）已被用作一种工具，用于研究疾病对骨骼、皮肤、肌腱和牙本质中ECM纳米级结构的影响。我们将这种方法扩展到椎间盘，并报告了在进行性椎间盘退变的小鼠模型中对亚微米尺度下ECM结构的首次定量分析。胶原D间距是原纤维水平纳米级结构的一个指标，观察到其值呈分布状态，总体平均值为62.5±2.5 nm。在退变椎间盘中，纤维环和髓核（NP）中的原纤维D间距分布均向更高值偏移（P<0.05）。在NP中观察到一种新的微观结构特征，由形成原纤维的基质包围的地形凹陷定义。随着退变，这些微观结构变得更多，形态从圆形（纵横比1.0±0.1）变为椭圆形（纵横比1.5±0.4），P<0.005。这些分析提供了椎间盘退变研究中历来缺失的尺寸尺度下椎间盘ECM的结构细节。从这些见解中获得的知识可能有助于开发新的疾病修饰疗法。
