Tang Tao, Zhu Zhengya, He Zhongyuan, Wang Fuan, Chen Lin, Li Jianfeng, Chen Hongkun, Zhou Jiaxiang, Wang Jianmin, Liu Shaoyu, Yao Yunfeng, Liu Xizhe, Zhou Zhiyu
Department of Orthopedic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Front Physiol. 2025 Mar 19;16:1561199. doi: 10.3389/fphys.2025.1561199. eCollection 2025.
Ossification of the posterior longitudinal ligaments (OPLL) is characterized by heterotopic ossification in the posterior longitudinal ligament of spine. Our earlier research found that mechanical stimulation enhances osteogenic differentiation in OPLL-derived ligament cells. Nevertheless, the function of hypermobility of the spine on ligament ossification remain unexplored .
We created the novel stimulation device to induce spinal hypermobility in mice with heterotopic ossification of the spine ligaments. The mice were randomly divided into three groups, control, slow hypermobility (SH) group and fast hypermobility (FH) group according to the frequency of spinal movement. Ligament ossification and changes in spinal range of motion (ROM) were assessed using micro-CT and X-rays. Morphological alterations were examined through HE staining. Behavioral evaluation was performed using the Basso Mouse Scale (BMS) score and inclined plane test (IPT). Immunofluorescence was employed to examine the expression of related proteins.
After 8 weeks, it showed increased ligament ossification and chondrocyte proliferation both in SH and FH group. After 16 weeks, The BMS score and IPT were lower both in the SH and FH group compared to the controls. Additionally, the ROM of cervicothoracic and thoracolumbar spine was lower in the FH group than in the controls. Immunofluorescence analysis revealed increased levels of SP7, RUNX2, OCN, DLX5, NOTCH1, and HES1 in the ligament tissues of the FH group compared to controls.
spinal hypermobility promotes the progression of ossification in mice with heterotopic ossification of the spine, shedding new light on the pathogenesis of OPLL.
后纵韧带骨化（OPLL）的特征是脊柱后纵韧带出现异位骨化。我们早期的研究发现，机械刺激可增强OPLL来源的韧带细胞的成骨分化。然而，脊柱活动过度对韧带骨化的作用仍未得到探索。
我们制作了新型刺激装置，以诱导脊柱韧带异位骨化的小鼠出现脊柱活动过度。根据脊柱运动频率，将小鼠随机分为三组：对照组、缓慢活动过度（SH）组和快速活动过度（FH）组。使用微型计算机断层扫描（micro-CT）和X射线评估韧带骨化和脊柱活动度（ROM）的变化。通过苏木精-伊红（HE）染色检查形态学改变。使用巴索小鼠量表（BMS）评分和斜面试验（IPT）进行行为评估。采用免疫荧光法检测相关蛋白的表达。
8周后，SH组和FH组均出现韧带骨化增加和软骨细胞增殖。16周后，与对照组相比，SH组和FH组的BMS评分和IPT均较低。此外，FH组颈胸段和胸腰段脊柱的ROM低于对照组。免疫荧光分析显示，与对照组相比，FH组韧带组织中SP7、RUNX2、骨钙素（OCN）、远端盒蛋白5（DLX5）、Notch1和HES1的水平升高。
脊柱活动过度促进了脊柱异位骨化小鼠的骨化进程，为OPLL的发病机制提供了新的线索。
