Kimura Atsushi, Taki Naoya, Hayashi Yukinori, Shiraishi Yasuyuki, Ohmori Tsukasa, Takeshita Katsushi
Department of Orthopaedics, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan.
Department of Biochemistry, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan.
Sci Rep. 2025 Jan 21;15(1):2608. doi: 10.1038/s41598-025-86847-6.
Ossification of the posterior longitudinal ligament of the vertebral column (OPLL) is a disease characterised by ectopic bone formation in the spinal ligament that causes progressive neurological impairment. However, there are no suitable treatments for OPLL. Here, we compared the general characteristics and haemostasis of patients with OPLL and those with cervical spondylotic myelopathy. Those with OPLL had significantly longer prothrombin times and lower plasma protein C concentrations, consistent with vitamin K deficiency. Therefore, we next characterised the effects of vitamin K supplementation on spinal hyperostosis in ttw mice, a model of cervical OPLL, by feeding them standard chow, vitamin K-deficient chow, or standard chow accompanied by biweekly vitamin K2 injections for 6 weeks. We found that vitamin K supplementation resulted in longer stride lengths and superior inter-limb coordination using footprint analysis. Furthermore, supplementation caused a significant reduction in ectopic calcification of the cervical ligaments of the mice, according to microcomputed tomography analysis. Finally, supplementation caused an increase in the number of osteochondrogenic cells expressing Gla-rich protein, an inhibitor of ectopic calcification, and increased the circulating concentration. Thus, vitamin K insufficiency may be involved in the pathogenesis of OPLL and supplementation may represent a novel treatment for this condition.
脊柱后纵韧带骨化（OPLL）是一种以脊柱韧带中异位骨形成导致进行性神经功能损害为特征的疾病。然而，目前尚无适用于OPLL的治疗方法。在此，我们比较了OPLL患者与脊髓型颈椎病患者的一般特征和止血情况。OPLL患者的凝血酶原时间显著延长，血浆蛋白C浓度降低，这与维生素K缺乏一致。因此，接下来我们通过给ttw小鼠（一种颈椎OPLL模型）喂食标准饲料、维生素K缺乏饲料或标准饲料并每两周注射一次维生素K2，持续6周，来研究补充维生素K对脊柱骨质增生的影响。通过足迹分析，我们发现补充维生素K可使步幅更长，四肢间协调性更好。此外，根据微型计算机断层扫描分析，补充维生素K可使小鼠颈椎韧带的异位钙化显著减少。最后，补充维生素K可使表达富含γ-羧基谷氨酸蛋白（一种异位钙化抑制剂）的骨软骨生成细胞数量增加，并使循环浓度升高。因此，维生素K缺乏可能参与了OPLL的发病机制，补充维生素K可能是治疗这种疾病的一种新方法。
