Gawri Rahul, Moir Janet, Ouellet Jean, Beckman Lorne, Steffen Thomas, Roughley Peter, Haglund Lisbet
Orthopaedic Research Laboratory, McGill University, Montreal, Quebec, Canada.
McGill Scoliosis and Spine Group, Montreal, Quebec, Canada.
PLoS One. 2014 Jul 3;9(7):e101233. doi: 10.1371/journal.pone.0101233. eCollection 2014.
A hallmark of early IVD degeneration is a decrease in proteoglycan content. Progression will eventually lead to matrix degradation, a decrease in weight bearing capacity and loss of disc height. In the final stages of IVD degradation, fissures appear in the annular ring allowing extrusion of the NP. It is crucial to understand the interplay between mechanobiology, disc composition and metabolism to be able to provide exercise recommendations to patients with early signs of disc degeneration. This study evaluates the effect of physiological loading compared to no loading on matrix homeostasis in bovine discs with induced degeneration. Bovine discs with trypsin-induced degeneration were cultured for 14 days in a bioreactor under dynamic loading with maintained metabolic activity. Chondroadherin abundance and structure was used to confirm that a functional matrix was preserved in the chosen loading environment. No change was observed in chondroadherin integrity and a non-significant increase in abundance was detected in trypsin-treated loaded discs compared to unloaded discs. The proteoglycan concentration in loaded trypsin-treated discs was significantly higher than in unloaded disc and the newly synthesised proteoglycans were of the same size range as those found in control samples. The proteoglycan showed an even distribution throughout the NP region, similar to that of control discs. Significantly more newly synthesised type II collagen was detected in trypsin-treated loaded discs compared to unloaded discs, demonstrating that physiological load not only stimulates aggrecan production, but also that of type II collagen. Taken together, this study shows that dynamic physiological load has the ability to repair the extracellular matrix depletion typical of early disc degeneration.
早期椎间盘退变的一个标志是蛋白聚糖含量的降低。退变进展最终会导致基质降解、承重能力下降和椎间盘高度丧失。在椎间盘退变的最后阶段,纤维环会出现裂隙,导致髓核突出。了解机械生物学、椎间盘组成和代谢之间的相互作用对于为有早期椎间盘退变迹象的患者提供运动建议至关重要。本研究评估了与无负荷相比,生理负荷对诱导退变的牛椎间盘基质稳态的影响。将胰蛋白酶诱导退变的牛椎间盘在生物反应器中动态加载培养14天,同时维持代谢活性。使用软骨粘连蛋白的丰度和结构来确认在所选加载环境中保留了功能性基质。与未加载的椎间盘相比,在胰蛋白酶处理的加载椎间盘中,未观察到软骨粘连蛋白完整性的变化,且丰度有不显著的增加。加载的胰蛋白酶处理椎间盘的蛋白聚糖浓度显著高于未加载的椎间盘,并且新合成的蛋白聚糖与对照样品中的蛋白聚糖大小范围相同。蛋白聚糖在整个髓核区域呈均匀分布,与对照椎间盘相似。与未加载的椎间盘相比,在胰蛋白酶处理的加载椎间盘中检测到显著更多的新合成II型胶原蛋白,表明生理负荷不仅刺激聚集蛋白聚糖的产生,也刺激II型胶原蛋白的产生。综上所述,本研究表明动态生理负荷有能力修复早期椎间盘退变典型的细胞外基质消耗。