University of Oulu

Ruiz Wills C, Foata B, González Ballester MÁ, Karppinen J and Noailly J (2018) Theoretical Explorations Generate New Hypotheses About the Role of the Cartilage Endplate in Early Intervertebral Disk Degeneration. Front. Physiol. 9:1210. doi: 10.3389/fphys.2018.01210

Theoretical explorations generate new hypotheses about the role of the cartilage endplate in early intervertebral disk degeneration

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Author: Ruiz Wills, Carlos1,2; Foata, Baptiste2; González Ballester, Miguel Á.1,3;
Organizations: 1BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra (UPF)
2Institute for Bioengineering of Catalonia (IBEC)
3Catalan Institution for Research and Advanced Studies (ICREA)
4Medical Research Center Oulu, Oulu University Hospital and University of Oulu
5Center for Life Course Health Research, Oulu University Hospital
6Finnish Institute of Occupational Health
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.9 MB)
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Language: English
Published: Frontiers Media, 2018
Publish Date: 2018-10-23


Altered cell nutrition in the intervertebral disk (IVD) is considered a main cause for disk degeneration (DD). The cartilage endplate (CEP) provides a major path for the diffusion of nutrients from the peripheral vasculature to the IVD nucleus pulposus (NP). In DD, sclerosis of the adjacent bony endplate is suggested to be responsible for decreased diffusion and disk cell nutrition. Yet, experimental evidence does not support this hypothesis. Hence, we evaluated how moderate CEP composition changes related to tissue degeneration can affect disk nutrition and cell viability. A novel composition-based permeability formulation was developed for the CEP, calibrated, validated, and used in a mechano-transport finite element IVD model. Fixed solute concentrations were applied at the outer surface of the annulus and the CEP, and three cycles of daily mechanical load were simulated. The CEP model indicated that CEP permeability increases with the degeneration/aging of the tissue, in accordance with recent measurements reported in the literature. Additionally, our results showed that CEP degeneration might be responsible for mechanical load-induced NP dehydration, which locally affects oxygen and lactate levels, and reduced glucose concentration by 16% in the NP-annulus transition zone. Remarkably, CEP degeneration was a condition sine-qua-non to provoke cell starvation and death, while simulating the effect of extracellular matrix depletion in DD. This theoretical study cast doubts about the paradigm that CEP calcification is needed to provoke cell starvation, and suggests an alternative path for DD whereby the early degradation of the CEP plays a key role.

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Series: Frontiers in physiology
ISSN: 1664-042X
ISSN-E: 1664-042X
ISSN-L: 1664-042X
Volume: 9
Article number: 1210
DOI: 10.3389/fphys.2018.01210
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: Funding was received from the European Commission (MySpine FP7-ICT-269909), and from the Spanish Ministry of Economy and Competitiveness (RYC-2015-18888, HOLOA-DPI2016-80283-C2-1-R and María de Maeztu Units of Excellence Program MDM-2015-0502). BF has collaborated to this work at IBEC with a studentship from the Erasmus mobility program.
Copyright information: © 2018 Ruiz Wills, Foata, González Ballester, Karppinen and Noailly. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.