LePage Emma C, Stoker Aaron M, Kuroki Keiichi, Cook James L
Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri, USA.
Department of Orthopaedic Surgery, Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri, USA.
J Orthop Res. 2021 Sep;39(9):1945-1954. doi: 10.1002/jor.24886. Epub 2020 Oct 29.
Many factors contribute to the development and progression of intervertebral disc (IVD) degeneration. This study was designed to assess the effects of compressive load magnitude on IVD metabolism. It was hypothesized that as load magnitude increased, there would be a significant increase in release of proinflammatory and degradative biomarkers, and a significant decrease in tissue proteoglycan (GAG) and collagen contents compared with unloaded controls. IVD whole organ functional spinal units (FSU) consisting of cranial and caudal body halves, cartilage endplates, and IVD (n = 36) were harvested from the tails of six Sprague Dawley rats, and FSUs were cultured at 0.0 MPa, 0.5 MPa, or 1.0 MPa at 0.5 Hz for 3 days. After culture, media were collected for biomarker analysis and FSUs were analyzed for extracellular matrix composition. Significant differences were determined using a one-way analysis of variance or Kruskal-Wallis test and post hoc analyses. Media concentrations of IFN-γ, IL-6, IL-1β, and MMP-8 were significantly higher in the 0.5 MPa compared with the 0.0 MPa group. Media concentrations of PGE2 and TIMP-1 were significantly higher in the 1.0 MPa group compared with the 0.0 MPa group, and media PGE2 was significantly higher in the 1.0 MPa group compared with the 0.5 MPa group. Media GAG content was significantly higher in the 1.0 MPa group compared with the 0.0 MPa group, and percent GAG in the tissue was significantly lower in 0.5 MPa and 1.0 MPa groups compared with the 0.0 MPa group. Clinical Significance: These data suggest that there are magnitude-dependent inflammatory and degradative IVD responses to cyclic loading, which may contribute to IVD degeneration.
许多因素导致椎间盘(IVD)退变的发生和进展。本研究旨在评估压缩负荷大小对IVD代谢的影响。研究假设,随着负荷大小增加,与未加载对照组相比,促炎和降解生物标志物的释放将显著增加,组织蛋白聚糖(GAG)和胶原蛋白含量将显著降低。从6只Sprague Dawley大鼠的尾部获取由头侧和尾侧半椎体、软骨终板和IVD组成的IVD全器官功能脊柱单元(FSU,n = 36),并将FSU在0.0MPa、0.5MPa或1.0MPa下以0.5Hz培养3天。培养后,收集培养基进行生物标志物分析,并对FSU进行细胞外基质组成分析。使用单因素方差分析或Kruskal-Wallis检验及事后分析确定显著差异。与0.0MPa组相比,0.5MPa组培养基中IFN-γ、IL-6、IL-1β和MMP-8的浓度显著更高。与0.0MPa组相比,1.0MPa组培养基中PGE2和TIMP-1的浓度显著更高,且与0.5MPa组相比,1.0MPa组培养基中PGE2显著更高。与0.0MPa组相比,1.0MPa组培养基中GAG含量显著更高,且与0.0MPa组相比,0.5MPa和1.0MPa组组织中GAG百分比显著更低。临床意义:这些数据表明,IVD对循环加载存在大小依赖性的炎症和降解反应,这可能导致IVD退变。