Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Division of Integrative Pathophysiology, Proteo-Science Center, Ehime University, Toon, Ehime, Japan.
Spine (Phila Pa 1976). 2019 Oct 15;44(20):E1172-E1180. doi: 10.1097/BRS.0000000000003089.
Case-control study of an animal model.
To investigate the factors that are upregulated and potentially related to degenerative changes in the ligamentum flavum (LF) upon mechanical stress concentration.
LF hypertrophy is reported to be associated with mechanical stress. However, few studies, using exhaustive analysis with control subjects, on the molecular mechanisms of LF hypertrophy have been published.
Fourteen rabbits were used for this study. The first group underwent L2-3 and L4-5 posterolateral fusion with instrumentation and resection of the L3-4 supraspinal muscle to concentrate the mechanical stress on L3-4, whereas the other group underwent a sham operation. The deep layer of the LF from L2-3 to L4-5 in both groups was harvested after 16 weeks. Gene expression was evaluated exhaustively using DNA microarray and real-time polymerase chain reaction (RT-PCR). Fibroblast growth factor 9 (FGF9) protein expression was subsequently examined by immunohistological staining.
A total of 680 genes were found to be upregulated upon mechanical stress concentration and downregulated upon mechanical shielding compared with those in the sham group. Functional annotation analysis revealed that these genes not only included those related to the extracellular matrix but also those related to certain FGF families. On RT-PCR validation and immunohistological analysis, we identified that the FGF9 protein increases in the LF upon mechanical stress, especially in the area wherein degenerative changes were frequently identified in the previous literature.
FGF9 and its pathway are suggested to contribute to the degenerative changes in the LF following mechanical stress. This finding will be helpful in further understanding the molecular mechanism of human LF degeneration.
N/A.
动物模型的病例对照研究。
研究机械应力集中时与黄韧带（LF）退行性改变相关的上调因素。
LF 肥大与机械应力有关。然而，很少有研究使用对照研究进行 LF 肥大的分子机制的详尽分析。
本研究使用了 14 只兔子。第一组进行 L2-3 和 L4-5 后路融合及器械固定，并切除 L3-4 棘上肌，以集中 L3-4 的机械应力，而另一组进行假手术。两组的 LF 深层（从 L2-3 到 L4-5）在 16 周后采集。使用 DNA 微阵列和实时聚合酶链反应（RT-PCR）进行了详尽的基因表达评估。随后通过免疫组织化学染色检查成纤维细胞生长因子 9（FGF9）蛋白的表达。
共发现 680 个基因在机械应力集中时上调，在机械屏蔽时下调，与假手术组相比。功能注释分析表明，这些基因不仅包括与细胞外基质相关的基因，还包括与某些 FGF 家族相关的基因。在 RT-PCR 验证和免疫组织化学分析中，我们发现 FGF9 蛋白在 LF 中随机械应力增加，尤其是在前人文献中常发现退行性改变的区域。
FGF9 及其途径可能导致 LF 在机械应力下发生退行性改变。这一发现有助于进一步了解人类 LF 退变的分子机制。
无。
