Research center of Spine Surgery, Department of Spine Surgery, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, PR China.
Research center of Spine Surgery, Department of Spine Surgery, Yijishan Hospital, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241001, PR China.
Life Sci. 2020 Oct 1;258:118213. doi: 10.1016/j.lfs.2020.118213. Epub 2020 Aug 5.
Intermittent cyclic tension stimulation(ICMT) was shown to promote degeneration of endplate chondrocytes and induce autophagy. However, enhancing autophagy can alleviate degeneration partly. Studies have shown that curcumin can induce autophagy and protect chondrocytes, we speculated that regulation of autophagy by curcumin might be an effective method to improve the stress resistance of endplate cartilage. In this study, human cervical endplate cartilage specimens were collected, and expression of autophagy markers was detected and compared.
Human cervical endplate chondrocytes were cultured to establish a tension-induced degeneration model, for which changes of functional metabolism and autophagy levels were detected under different tension loading conditions. Changes in functional metabolism of endplate chondrocytes were observed under high-intensity tension loading in the presence of inhibitors, inducers, and curcumin to regulate the autophagy level of cells. In addition, a rat model of lumbar instability was established to observe the degeneration of lumbar disc after curcumin administration.
Through a series of experiments, we found that low-intensity tension stimulation can maintain a stable phenotype of endplate chondrocytes, but high-intensity tension stimulation has a negative effect. Moreover, with increasing tension intensity, the degree of degeneration of endplate chondrocytes was gradually aggravated and the level of autophagy increased. Besides, curcumin upregulated autophagy, inhibited apoptosis, and reduced phenotype loss of endplate chondrocytes induced by high-intensity tension loading, thereby relieving intervertebral disc degeneration induced by mechanical imbalance.
Curcumin mediated autophagy and enhanced the adaptability of endplate chondrocytes to high-intensity tension load, thereby relieving intervertebral disc degeneration.
间歇性循环张力刺激（ICMT）已被证明可促进终板软骨细胞退化并诱导自噬。然而，增强自噬可以部分缓解退化。研究表明姜黄素可以诱导自噬并保护软骨细胞，我们推测姜黄素对自噬的调节可能是改善终板软骨抗应激能力的有效方法。本研究中，我们收集了人颈椎终板软骨标本，检测并比较了自噬标志物的表达。
培养人颈椎终板软骨细胞，建立张力诱导的退变模型，在不同张力加载条件下检测其功能代谢和自噬水平的变化。在高张应力加载下，通过抑制剂、诱导剂和姜黄素调节细胞自噬水平，观察终板软骨细胞功能代谢的变化。此外，建立大鼠腰椎不稳模型，观察姜黄素给药后腰椎间盘的退变。
通过一系列实验，我们发现低张应力刺激可以维持终板软骨细胞的稳定表型，但高张应力刺激则具有负面影响。此外，随着张力强度的增加，终板软骨细胞的退变程度逐渐加重，自噬水平也逐渐升高。此外，姜黄素上调自噬，抑制细胞凋亡，减少高强度张力负荷诱导的终板软骨细胞表型丧失，从而缓解机械失衡引起的椎间盘退变。
姜黄素介导的自噬增强了终板软骨细胞对高强度张力负荷的适应性，从而缓解椎间盘退变。
