Diurnal Asymmetric Loading Modulates Cell Phenotype in Intervertebral Disc

IF 3.4 3区 医学 Q1 ORTHOPEDICS
JOR Spine Pub Date : 2025-05-07 DOI:10.1002/jsp2.70068
Ying Zhang, Jianbiao Xu, Zhiyu Zhou, R. Geoff Richards, Mauro Alini, Sibylle Grad, Zhen Li
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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

Abstract Image

昼夜不对称负荷调节椎间盘细胞表型
目的本研究在离体模型中验证了不对称动态载荷单独或联合静态载荷影响椎间盘(IVD)细胞形态学和生物学特性的假设。方法将牛尾部ivd分为4组:(1)平行动载(1 h) +自由肿胀(23 h);(2)并联动载(1 h) +静载(23 h);(3)楔形动载荷(1 h) +自由膨胀(23 h);(4)楔形动荷载(1 h) +静荷载(23 h)。通过测量高度损失和组织学染色来评估IVD结构。IVD组织和细胞反应也被测量。结果每日动态加载和自由肿胀恢复可使器官培养盘细胞活力和基因表达维持在生理水平。每日动态负荷之后是静态负荷导致退行性条件,如较低的细胞活力,较低的合成代谢和较高的分解代谢基因表达所示。在动态负荷+自由肿胀负荷下,与第0天健康对照组相比,楔形负荷上调了纤维环(AF)凹凸侧的ACAN基因表达水平。在动载+静载模式下,楔形组的凹凸面MMP1基因表达呈增加趋势;楔形组凹侧MMP13基因表达呈增加趋势。楔形组髓核(NP)组织有向凸侧突出的趋势。结论在体外培养模型中,先动态加载后持续静态加载可负向调节IVD细胞的表型。与动载后的自由肿胀治疗相比,物理治疗减少IVD上的应力,即使是暂时的,也可能有助于防止畸形和退变的加速。这些结果表明,不对称加载后再进行静态加载可用于模拟脊柱畸形IVD的病理变化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
JOR Spine
JOR Spine ORTHOPEDICS-
CiteScore
6.40
自引率
18.90%
发文量
42
审稿时长
10 weeks
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