Abstract
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.
Highlights
One of the principal causes of intervertebral disk (IVD) degeneration (DD) in the lumbar spine is suggested to be the alteration of the nutrient supply to disk cells (Urban and Roberts, 2003), which leads to local low levels of oxygen and glucose, and high levels of lactate, i.e., acidic pH
The obtained parameters B and C had negative values, and the absolute value of the former was much larger than that of the latter. Using these parameters in Equation 1 and simulating a gradient of composition from the nucleus pulposus (NP) to the cartilage endplate (CEP) led to the CEP permeability distribution shown in Figure 2, where the permeability increased from the NP to the bony endplate (BEP)
The negative signs obtained for parameters B and C reflect the correlations found by Williamson et al (2001) for bovine articular cartilage, where increased proteoglycan and collagen contents led to reduced hydraulic permeability
Summary
One of the principal causes of intervertebral disk (IVD) degeneration (DD) in the lumbar spine is suggested to be the alteration of the nutrient supply to disk cells (Urban and Roberts, 2003), which leads to local low levels of oxygen and glucose, and high levels of lactate, i.e., acidic pH. Nutrients can reach IVD cells from the peripheral blood supply, either through the outer annulus fibrosus (AF) or through the cartilage endplate (CEP) (Urban et al, 2004; Shankar et al, 2009), adjacent to the vertebral subchondral bone, i.e., the bony endplate (BEP). The solutes such as oxygen and glucose are transported into the disk through the CEP, and their availability is regulated by the bone marrow contact channels that cross the BEP (Benneker et al, 2005a,b). CEP calcification is unlikely to be involved in early DD processes
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