Department of Neurosurgery, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Int J Mol Sci. 2023 Feb 2;24(3):2872. doi: 10.3390/ijms24032872.
Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.
为了阐明发病机制，我们分析了取自颈椎间盘突出症（对照组，Ctrl）和手术患者后纵韧带骨化（OPLL）组织的原发性脊柱韧带源性细胞（SLDCs）。在这里，我们发现铁蛋白水平降低和碱性磷酸酶（ALP）水平升高，即骨形成标志物，可促使 OPLL 中的 SLDC 成骨。Ctrl 和 OPLL 组的 SLDCs 符合间充质干细胞/基质细胞的定义。RNA 测序显示，OPLL 组的氧化磷酸化和柠檬酸循环途径上调。OPLL 组的 SLDCs 显示线粒体质量增加，线粒体活性氧（ROS）产生增加，铁蛋白等 ROS 清除剂水平降低。ROS 和铁蛋白水平呈时间依赖性上调和下调，这两种分子均抑制 ALP。添加脱铁蛋白可减轻成骨作用。我们提出，提高铁蛋白水平可能会缓解 OPLL 中的成骨作用。
