Repetitive Strikes Loading Organ Culture Model to Investigate the Biological and Biomechanical Responses of the Intervertebral Disc

Overview

Journal JOR Spine

Specialty Orthopedics

Date 2024 Jan 22

PMID 38249719

Authors

Jiaxiang Zhou

Jianmin Wang

Jianfeng Li

Zhengya Zhu

Zhongyuan He

Junhong Li

Tao Tang

Hongkun Chen

Yukun Du

Zhen Li

Manman Gao

Zhiyu Zhou

Yongming Xi

Affiliations

Soon will be listed here.

Abstract

Background: Disc degeneration is associated with repetitive violent injuries. This study aims to explore the impact of repetitive strikes loading on the biology and biomechanics of intervertebral discs (IVDs) using an organ culture model.

Methods: IVDs from the bovine tail were isolated and cultured in a bioreactor, with exposure to various loading conditions. The control group was subjected to physiological loading, while the model group was exposed to either one strike loading (compression at 38% of IVD height) or repetitive one strike loading (compression at 38% of IVD height). Disc height and dynamic compressive stiffness were measured after overnight swelling and loading. Furthermore, histological morphology, cell viability, and gene expression were analyzed on Day 32. Glycosaminoglycan (GAG) and nitric oxide (NO) release in conditioned medium were also analyzed.

Results: The repetitive one strike group exhibited early disc degeneration, characterized by decreased dynamic compression stiffness, the presence of annulus fibrosus clefts, and degradation of the extracellular matrix. Additionally, this group demonstrated significantly higher levels of cell death ( < 0.05) and glycosaminoglycan (GAG) release ( < 0.05) compared to the control group. Furthermore, upregulation of MMP1, MMP13, and ADAMTS5 was observed in both nucleus pulposus (NP) and annulus fibrosus (AF) tissues of the repetitive one strike group ( < 0.05). The one strike group exhibited annulus fibrosus clefts but showed no gene expression changes compared to the control group.

Conclusions: This study shows that repetitive violent injuries lead to the degeneration of a healthy bovine IVDs, thereby providing new insights into early-stage disc degeneration.

Citing Articles

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Holsgrove T, Ebisch I, Lazaro-Pacheco D JOR Spine. 2025; 8(1):e70024.

PMID: 39968355 PMC: 11834163. DOI: 10.1002/jsp2.70024.

Repetitive strikes loading organ culture model to investigate the biological and biomechanical responses of the intervertebral disc.

Zhou J, Wang J, Li J, Zhu Z, He Z, Li J JOR Spine. 2024; 7(1):e1314.

PMID: 38249719 PMC: 10797252. DOI: 10.1002/jsp2.1314.

References

Sitte I, Kathrein A, Pfaller K, Pedross F, Roberts S . Intervertebral disc cell death in the porcine and human injured cervical spine after trauma: a histological and ultrastructural study. Spine (Phila Pa 1976). 2009; 34(2):131-40. DOI: 10.1097/BRS.0b013e31818edcd6. View

Giers M, Munter B, Eyster K, Ide G, Newcomb A, Lehrman J . Biomechanical and Endplate Effects on Nutrient Transport in the Intervertebral Disc. World Neurosurg. 2016; 99:395-402. DOI: 10.1016/j.wneu.2016.12.041. View

Lazaro-Pacheco D, Mohseni M, Rudd S, Cooper-White J, Holsgrove T . The role of biomechanical factors in models of intervertebral disc degeneration across multiple length scales. APL Bioeng. 2023; 7(2):021501. PMC: 10168717. DOI: 10.1063/5.0137698. View

Gause P, Godinsky R, Burns K, Dohring E . Lumbar Disk Herniations and Radiculopathy in Athletes. Clin Sports Med. 2021; 40(3):501-511. DOI: 10.1016/j.csm.2021.04.001. View

Chen X, Chen H, Li B, Xiao Z, Zhou Y, Tian W . Dynamic elastic modulus assessment of the early degeneration model of an intervertebral disc in cynomolgus monkeys with one strike loading. Comput Methods Programs Biomed. 2022; 224:106982. DOI: 10.1016/j.cmpb.2022.106982. View

Kurakawa T, Kakutani K, Morita Y, Kato Y, Yurube T, Hirata H . Functional impact of integrin α5β1 on the homeostasis of intervertebral discs: a study of mechanotransduction pathways using a novel dynamic loading organ culture system. Spine J. 2014; 15(3):417-26. PMC: 5673479. DOI: 10.1016/j.spinee.2014.12.143. View

Bai X, Wang D, Zhou M, Xu C, Li W, Tao H . Noninvasive cumulative axial load may induce intervertebral disc degeneration-A potential rabbit model. Exp Ther Med. 2017; 13(4):1438-1446. PMC: 5377280. DOI: 10.3892/etm.2017.4148. View

Secerovic A, Ristaniemi A, Cui S, Li Z, Soubrier A, Alini M . Toward the Next Generation of Spine Bioreactors: Validation of an Ex Vivo Intervertebral Disc Organ Model and Customized Specimen Holder for Multiaxial Loading. ACS Biomater Sci Eng. 2022; 8(9):3969-3976. PMC: 9472220. DOI: 10.1021/acsbiomaterials.2c00330. View

Ding S, Zhang T, Zhang Q, Ding W, Li Z, Han G . Excessive mechanical strain accelerates intervertebral disc degeneration by disrupting intrinsic circadian rhythm. Exp Mol Med. 2021; 53(12):1911-1923. PMC: 8741925. DOI: 10.1038/s12276-021-00716-6. View

10.

Yang M, Xiang D, Wang S, Liu W . In Vitro Studies for Investigating Creep of Intervertebral Discs under Axial Compression: A Review of Testing Environment and Results. Materials (Basel). 2022; 15(7). PMC: 9000064. DOI: 10.3390/ma15072500. View

11.

Cieza A, Causey K, Kamenov K, Wulf Hanson S, Chatterji S, Vos T . Global estimates of the need for rehabilitation based on the Global Burden of Disease study 2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020; 396(10267):2006-2017. PMC: 7811204. DOI: 10.1016/S0140-6736(20)32340-0. View

12.

Haschtmann D, Stoyanov J, Gedet P, Ferguson S . Vertebral endplate trauma induces disc cell apoptosis and promotes organ degeneration in vitro. Eur Spine J. 2007; 17(2):289-99. PMC: 2365539. DOI: 10.1007/s00586-007-0509-5. View

13.

Salzer E, Mouser V, Bulsink J, Tryfonidou M, Ito K . Dynamic loading leads to increased metabolic activity and spatial redistribution of viable cell density in nucleus pulposus tissue. JOR Spine. 2023; 6(1):e1240. PMC: 10041377. DOI: 10.1002/jsp2.1240. View

14.

Ma J, Stefanoska D, Grad S, Alini M, Peroglio M . Direct and Intervertebral Disc-Mediated Sensitization of Dorsal Root Ganglion Neurons by Hypoxia and Low pH. Neurospine. 2020; 17(1):42-59. PMC: 7136118. DOI: 10.14245/ns.2040052.026. View

15.

Elmounedi N, Bahloul W, Aoui M, Sahnoun N, Ellouz Z, Keskes H . Original animal model of lumbar disc degeneration. Libyan J Med. 2023; 18(1):2212481. PMC: 10190185. DOI: 10.1080/19932820.2023.2212481. View

16.

Cui S, Li W, Teixeira G, Neidlinger-Wilke C, Wilke H, Haglund L . Neoepitope fragments as biomarkers for different phenotypes of intervertebral disc degeneration. JOR Spine. 2022; 5(3):e1215. PMC: 9520770. DOI: 10.1002/jsp2.1215. View

17.

Feng C, Yang M, Zhang Y, Lan M, Huang B, Liu H . Cyclic mechanical tension reinforces DNA damage and activates the p53-p21-Rb pathway to induce premature senescence of nucleus pulposus cells. Int J Mol Med. 2018; 41(6):3316-3326. PMC: 5881642. DOI: 10.3892/ijmm.2018.3522. View

18.

Silagi E, Shapiro I, Risbud M . Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration. Matrix Biol. 2018; 71-72:368-379. PMC: 6119535. DOI: 10.1016/j.matbio.2018.02.025. View

19.

Zhou J, Wang J, Li J, Zhu Z, He Z, Li J . Repetitive strikes loading organ culture model to investigate the biological and biomechanical responses of the intervertebral disc. JOR Spine. 2024; 7(1):e1314. PMC: 10797252. DOI: 10.1002/jsp2.1314. View

20.

Molladavoodi S, McMorran J, Gregory D . Mechanobiology of annulus fibrosus and nucleus pulposus cells in intervertebral discs. Cell Tissue Res. 2019; 379(3):429-444. DOI: 10.1007/s00441-019-03136-1. View