Contribution of the Endplates to Disc Degeneration

Fields, Aaron J.; Ballatori, Alexander; Liebenberg, Ellen; Lotz, Jeffrey C.

doi:10.1007/s40610-018-0105-y

Cited by 93 publications

(91 citation statements)

References 125 publications

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“…Cells inside the nucleus pulposus (NP) mainly rely on nutrient transport to and from the vertebral capillaries, 9,10 which can be compromised by several factors. The vertebral capillaries penetrate pores in the bony endplate and terminate adjacent to the cartilage endplate (CEP) 11,12 (CEP; Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy

Wong

Sampson

Bell-Briones

et al. 2019

Osteoarthritis and Cartilage

115

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Fourier transform infrared imaging Nutrient transport Nucleus pulposus cell Low back pain s u m m a r y Objective: Intradiscal biologic therapy is a promising strategy for managing intervertebral disc degeneration. However, these therapies require a rich nutrient supply, which may be limited by the transport properties of the cartilage endplate (CEP). This study investigated how fluctuations in CEP transport properties impact nutrient diffusion and disc cell survival and function. Design: Human CEP tissues harvested from six fresh cadaveric lumbar spines (38e66 years old) were placed at the open sides of diffusion chambers. Bovine nucleus pulposus (NP) cells cultured inside the chambers were nourished exclusively by nutrients diffusing through the CEP tissues. After 72 h in culture, depth-dependent NP cell viability and gene expression were measured, and related to CEP transport properties and biochemical composition determined using fluorescence recovery after photobleaching and Fourier transform infrared (FTIR) spectroscopy. Results: Solute diffusivity varied nearly 4-fold amongst the CEPs studied, and chambers with the least permeable CEPs appeared to have lower aggrecan, collagen-2, and matrix metalloproteinase-2 gene expression, as well as a significantly shorter viable distance from the CEP/nutrient interface. Increasing chamber cell density shortened the viable distance; however, this effect was lost for low-diffusivity CEPs, which suggests that these CEPs may not provide enough nutrient diffusion to satisfy cell demands. Solute diffusivity in the CEP was associated with biochemical composition: low-diffusivity CEPs had greater amounts of collagen and aggrecan, more mineral, and lower cross-link maturity. Conclusions: CEP transport properties dramatically affect NP cell survival/function. Degeneration-related CEP matrix changes could hinder the success of biologic therapies that require increased nutrient supply.

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Section: Introductionmentioning

confidence: 99%

Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy

Wong

Sampson

Bell-Briones

et al. 2019

Osteoarthritis and Cartilage

115

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“…For example, nutrients entering the disc and exiting metabolites must diffuse through the cartilage endplates (CEP), and diffusion could be hindered by age- or degeneration-related changes to the CEP matrix, including dehydration [14], mineralization [15–17], and fibrosis [14, 17, 18]. In addition to altering the mechanical functionality of the CEP [19], which is also physiologically important [20, 21], these matrix changes impact CEP biotransport functionality too. Specifically, dehydration prevents solutes from diffusing freely within the CEP; and increased deposition of proteoglycan, collagen, and mineral limits the amount of pore space available to solutes [22, 23].…”

Section: Introductionmentioning

confidence: 99%

Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition

et al. 2019

Self Cite

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Poor solute transport through the cartilage endplate (CEP) impairs disc nutrition and could be a key factor that limits the success of intradiscal biologic therapies. Here we demonstrate that treating the CEP with matrix metalloproteinase-8 (MMP-8) reduces the matrix constituents that impede solute uptake and thereby improves nutrient diffusion. Human CEP tissues harvested from four fresh cadaveric lumbar spines (age range: 38–66 years old) were treated with MMP-8. Treatment caused a dose-dependent reduction in sGAG, localized reductions to the amount of collagen, and alterations to collagen structure. These matrix modifications corresponded with 16–24% increases in the uptake of a small solute (376 Da). Interestingly, the effects of MMP-8 treatment depended on the extent of non-enzymatic glycation: treated CEPs with high concentrations of advanced glycation end products (AGEs) exhibited the lowest uptake compared to treated CEPs with low concentrations of AGEs. Moreover, AGE concentrations were donor-specific, and the donor tissues with the highest AGE concentrations appeared to have lower uptake than would be expected based on the initial amounts of collagen and sGAG. Finally, increasing solute uptake in the CEP improved cell viability inside diffusion chambers, which supports the nutritional relevance of enhancing the transport properties of the CEP. Taken together, our results provide new insights and in vitro proof-of-concept for a treatment approach that could improve disc nutrition for biologic therapy: specifically, matrix reduction by MMP-8 can enhance solute uptake and nutrient diffusion through the CEP, and AGE concentration appears to be an important, patient-specific factor that influences the efficacy of this approach.

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“…The endplate is a layered composite material composed of semiporous thickened cancellous bone (0.6-1 mm) and transparent cartilage (0.2-0.8 mm) [8]. Because of its unique anatomical morphology and material properties, the cartilage endplate has two important functions: biological transport and stress conduction [9]. On the one hand, the intervertebral disc is the largest avascular structure in the human body, and the nucleus pulposus cells almost completely depend on the nutrients provided by the capillary bed of the vertebral body near the endplate.…”

Section: Discussionmentioning

confidence: 99%

Effects of Endplate Healing Morphology on Intervertebral Disc Degeneration after Pedicle Screw Fixation for Thoracolumbar Fractures

Ren

Liu

et al. 2020

Preprint

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Background: The cartilage endplate plays an important role in the stress distribution and nutrition metabolism of intervertebral disc. The healing morphology of the endplate after spinal fracture and its effect on the intervertebral disc degeneration are still unclear. Methods: 51 patients with single-level thoracolumbar fractures underwent posterior open reduction and pedicle screw fixation. Combined with the initial CT and MRI images, the endplate injury was defined as three types, which are unilateral endplate injury, bilateral endplate injury and no endplate injury. According to the location of the injury in the endplate, it was further divided into endplate central injury and endplate peripheral injury. The degree of post-traumatic disc lesions and disc degeneration during follow-up were classified based on the Sander classification and the Pfirrmann classification, respectively. According to the T1 image of MRI in the final follow-up, the healing morphology of endplates was classified into three types including the increased endplate curvature, the irregular healing and the traumatic Schmorl nodes. Results: Cartilage endplate fractures are closely related to the degree of degeneration of the intervertebral disc (P=0.003). Injuries in different parts of the endplate have no significant effect on the intervertebral disc degeneration (P=0.204). The healing morphology after endplate fracture significantly affected the degree of intervertebral disc degeneration (P=0.001). The comparison of groups showed that the effects of irregular healing and traumatic Schmorl nodes on disc degeneration were not statistically different, but were significantly different from those with increased curvature. Conclusions: Increased endplate curvature, irregular healing and traumatic Schmorl nodes are three common forms of healing. The irregular healing and the traumatic Schmorl nodes are closely related to intervertebral disc degeneration. The existence and severity of the endplate injury can provide valuable information for individualized clinical decision-making processes.

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Contribution of the Endplates to Disc Degeneration

Cited by 93 publications

References 125 publications

Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy

Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy

Matrix modification for enhancing the transport properties of the human cartilage endplate to improve disc nutrition

Effects of Endplate Healing Morphology on Intervertebral Disc Degeneration after Pedicle Screw Fixation for Thoracolumbar Fractures

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