Zhang Ying, Xu Jianbiao, Zhou Zhiyu, Richards R Geoff, Alini Mauro, Grad Sibylle, Li Zhen
AO Research Institute Davos Davos Switzerland.
Department of Orthopedics, Spine Center Changzheng Hospital, Naval Medical University Shanghai China.
JOR Spine. 2025 May 7;8(2):e70068. doi: 10.1002/jsp2.70068. eCollection 2025 Jun.
This study tested the hypothesis that asymmetric dynamic loading alone or in combination with static loading influences the morphological and biological characteristics of the intervertebral disc (IVD) cells in an ex vivo model.
Bovine caudal IVDs were assigned to four groups: (1) Parallel dynamic load (1 h) + free swelling (23 h); (2) Parallel dynamic load (1 h) + static load (23 h); (3) Wedge dynamic load (1 h) + free swelling (23 h); (4) Wedge dynamic load (1 h) + static load (23 h). IVD structure was assessed with measurements of height loss and histological staining. IVD tissue and cellular responses were also measured.
Diurnal dynamic loading and free swelling recovery could maintain cell viability and the gene expression of organ-cultured discs at their physiological level. Diurnal dynamic loading followed by static loading resulted in a degenerative condition, as indicated by lower cell viability, lower anabolic, and higher catabolic gene expression. Under the dynamic load + free swelling load regime, wedge loading upregulated the ACAN gene expression level in the concave and convex sides of the annulus fibrosus (AF) compared with day 0 healthy control. Under the dynamic load + static loading regime, the MMP1 gene expression showed a trend of increase in the concave and convex sides of the wedge group; the MMP13 gene expression showed a trend of increase in the concave side of the wedge group. The nucleus pulposus (NP) tissue in the wedge group showed a trend of protrusion toward the convex side.
Dynamic loading followed by continuous static loading negatively modulates the phenotype of IVD cells in this organ culture model. Comparable to the free swelling treatment after dynamic loading, physical treatment to reduce the stress on the IVD, even temporarily, may help to prevent the acceleration of deformity and degeneration. These results indicate that asymmetric loading followed by static loading may be used to mimic pathological changes of the IVD in spinal deformity.
本研究检验了以下假设，即单独的不对称动态负荷或与静态负荷联合使用会在体外模型中影响椎间盘（IVD）细胞的形态和生物学特性。
将牛尾椎间盘分为四组：（1）平行动态负荷（1小时）+自由肿胀（23小时）；（2）平行动态负荷（1小时）+静态负荷（23小时）；（3）楔形动态负荷（1小时）+自由肿胀（23小时）；（4）楔形动态负荷（1小时）+静态负荷（23小时）。通过测量高度损失和组织学染色评估椎间盘结构。还测量了椎间盘组织和细胞反应。
昼夜动态负荷和自由肿胀恢复可将器官培养椎间盘的细胞活力和基因表达维持在生理水平。昼夜动态负荷后再进行静态负荷导致退变状态，表现为细胞活力降低、合成代谢降低和分解代谢基因表达升高。在动态负荷+自由肿胀负荷方案下，与第0天健康对照相比，楔形负荷上调了纤维环（AF）凹侧和凸侧的ACAN基因表达水平。在动态负荷+静态负荷方案下，MMP1基因表达在楔形组的凹侧和凸侧呈增加趋势；MMP13基因表达在楔形组的凹侧呈增加趋势。楔形组的髓核（NP）组织有向凸侧突出的趋势。
在该器官培养模型中，动态负荷后持续静态负荷对IVD细胞表型产生负向调节作用。与动态负荷后的自由肿胀处理类似，即使是暂时减轻IVD应力的物理处理，也可能有助于防止畸形和退变加速。这些结果表明，动态负荷后再进行静态负荷可用于模拟脊柱畸形中IVD的病理变化。
