Department of Orthopaedic Surgery, VU University Medical Center, Amsterdam, The Netherlands.
PLoS One. 2013 Apr 30;8(4):e62411. doi: 10.1371/journal.pone.0062411. Print 2013.
Mechanical overloading of the spine is associated with low back pain and intervertebral disc (IVD) degeneration. How excessive loading elicits degenerative changes in the IVD is poorly understood. Comprehensive knowledge of the interaction between mechanical loading, cell responses and changes in the extracellular matrix of the disc is needed in order to successfully intervene in this process. The purpose of the current study was to investigate whether dynamic and static overloading affect caprine lumbar discs differently and what mechanisms lead to mechanically induced IVD degeneration. Lumbar caprine IVDs (n = 175) were cultured 7, 14 and 21 days under simulated-physiological loading (control), high dynamic or high static loading. Axial deformation and stiffness were continuously measured. Cell viability, cell density, and gene expression were assessed in the nucleus, inner- and outer annulus. The extracellular matrix (ECM) was analyzed for water, glycosaminoglycan and collagen content. IVD height loss and changes in axial deformation were gradual with dynamic and acute with static overloading. Dynamic overloading caused cell death in all IVD regions, whereas static overloading mostly affected the outer annulus. IVDs expression of catabolic and inflammation-related genes was up-regulated directly, whereas loss of water and glycosaminoglycan were significant only after 21 days. Static and dynamic overloading both induced pathological changes to caprine lumbar IVDs within 21 days. The mechanism by which they inflict biomechanical, cellular, and extracellular changes to the nucleus and annulus differed. The described cascades provide leads for the development of new pharmacological and rehabilitative therapies to halt the progression of DDD.
脊柱的机械性过载与下腰痛和椎间盘（IVD）退变有关。过度负荷如何引起 IVD 的退行性变化尚不清楚。为了成功干预这一过程，需要全面了解机械负荷、细胞反应和椎间盘细胞外基质的变化之间的相互作用。本研究的目的是研究动态和静态过载是否对山羊腰椎间盘有不同的影响，以及导致机械性 IVD 退变的机制。在模拟生理负荷（对照）、高动态或高静态负荷下，培养山羊腰椎间盘（n = 175）7、14 和 21 天。连续测量轴向变形和刚度。评估核、内环和外环的细胞活力、细胞密度和基因表达。分析细胞外基质（ECM）的含水量、糖胺聚糖和胶原含量。IVD 高度损失和轴向变形的变化随动态过载而逐渐发生，随静态过载而急性发生。动态过载导致所有 IVD 区域的细胞死亡，而静态过载主要影响外环。IVD 中分解代谢和炎症相关基因的表达直接上调，而只有在 21 天后才会出现明显的水分和糖胺聚糖损失。在 21 天内，静态和动态过载都会导致山羊腰椎 IVD 发生病理变化。它们对核和环施加生物力学、细胞和细胞外变化的机制不同。所描述的级联反应为开发新的药理学和康复疗法以阻止 DDD 的进展提供了线索。
