Nutrition of the Intervertebral Disc: Solute Transport and Metabolism

Holm, Sture; Maroudas, Alice; Urban, Jill; Selstam, Gunnar; Nachemson, Alf

doi:10.3109/03008208109152130

Cited by 473 publications

(369 citation statements)

References 22 publications

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“…Glucose on the other hand is present in sufficient quantities in the construct for both mixed and static cases ( Figure 7). It has been shown previously that fluid velocities within the construct induced by cyclic compression are too low to influence the transport of small solutes significantly (53,56). Therefore, as a first approximation only the effect of the presence of the loading platen was investigated in the present study.…”

Section: Discussionmentioning

confidence: 98%

Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Sengers

Donkelaar

Oomens

et al. 2008

Biotechnol Progress

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Different culture conditions for cartilage tissue engineering were evaluated with respect to the supply of oxygen and glucose and the accumulation of lactate. A computational approach was adopted in which the culture configurations were modeled as a batch process and transport was considered within constructs seeded at high cell concentrations and of clinically relevant dimensions. To assess the extent to which mass transfer can be influenced theoretically, extreme cases were distinguished in which the culture medium surrounding the construct was assumed either completely static or well mixed and fully oxygenated. It can be concluded that severe oxygen depletion and lactate accumulation can occur within constructs for cartilage tissue engineering. However, the results also indicate that transport restrictions are not insurmountable, providing that the medium is well homogenized and oxygenated and the construct's surfaces are sufficiently exposed to the medium. The large variation in uptake rates of chondrocytes indicates that for any specific application the quantification of cellular utilization rates, depending on the cell source and culture conditions, is an essential starting point for optimizing culture protocols.

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Section: Discussionmentioning

confidence: 98%

Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Sengers

Donkelaar

Oomens

et al. 2008

Biotechnol Progress

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“…The nutritional status of the cells of the central nucleus pulposus is precarious; the oxygen tension field as well as the concentration gradient of glucose is very steep and the cells in the central region of the tissue may not be able to satisfy their requirements (10). Cell necrosis in the disc due to lack of substrates such as oxygen and glucose may lead to severe disc degeneration.…”

Section: Introductionmentioning

confidence: 99%

Studies of the Lumbar Vertebral End-plate Region in the Pig

Törner¹,

Holm²

1985

Upsala Journal of Medical Sciences

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The vertebral end-plates and the epiphyses from the lumbar region of the spine in juvenile pigs were studied. Cell density of the hyaline cartilage of the vertebral bodies was measured as well as cartilage thickness.The relative bone content in the region of the nucleus pulposus was calculated.A certain negative interrelationship between cartilage thickness and cell density of the hyaline cartilage of the vertebral bodies was found.The relative bone content of the cranial epiphysis was higher than that of the caudal epiphysis in the same motion segment at all levels of the lumbar spine. The difference was pronounced down to 2 mm from the cartilagelbone interface.

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“…In specialized tissues such as the intervertebral disc, the mechanism by which cells conserve energy has received little attention. Nonetheless, since the gelatinous center, the nucleus pulposus, has no vascular supply (4,5), it is probable that ATP is generated by anaerobic glycolysis (6,7). Regulation of glycolysis is mediated by hypoxia-inducible factor 1␣ (HIF-1␣), a key transcription factor that is expressed by the nucleus pulposus cells (8).…”

mentioning

confidence: 99%

Cited2 modulates hypoxia‐inducible factor–dependent expression of vascular endothelial growth factor in nucleus pulposus cells of the rat intervertebral disc

Agrawal¹,

Gajghate²,

Smith³

et al. 2008

Arthritis & Rheumatism

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Objective. To determine whether nucleus pulposus cells of the intervertebral disc express hypoxiainducible factor 2␣ (HIF-2␣), and to assess the role of HIF-1 and HIF-2 in controlling cited2 and vascular endothelial growth factor (VEGF) expression.Methods. Rat cells were cultured under normoxic (21% O 2 ) or hypoxic (2% O 2 ) conditions, and expression and promoter activity of HIF-2 target genes were evaluated. Gain-or loss-of-function experiments were performed to investigate the contribution of HIF isoforms to cited2 activity as well as the role of cited2 in regulating VEGF expression.Results. We found that HIF-2␣ protein was expressed in vivo and that protein and messenger RNA expression were similar under both normoxic and hypoxic conditions. However, there was a significant increase in HIF-2␣ transactivation under hypoxic conditions. With respect to functional activity, unlike the case in most other tissues, HIF-2 failed to increase the transcriptional activities of superoxide dismutase 2 and frataxin, 2 common target genes involved in radical dismutation. However, under hypoxic conditions, HIF-2 preferentially regulated the expression and promoter activity of cited2, a p300 binding protein. When HIF-2␣ or HIF-1␣ was suppressed, cited2 promoter activity was inhibited. Finally, we showed that forced expression or suppression of cited2 resulted in corresponding changes in expression of VEGF, a common target gene for HIF-1 and HIF-2 in the nucleus pulposus cells.Conclusion. Results of this study indicate that in nucleus pulposus cells, HIF-2 and HIF-1 modulate their own transcriptional activity through cited2. We suggest that the 2 arms of the regulatory circuit serve to maintain survival activities and inhibit angiogenesis in the healthy disc.

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Nutrition of the Intervertebral Disc: Solute Transport and Metabolism

Cited by 473 publications

References 22 publications

Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Computational Study of Culture Conditions and Nutrient Supply in Cartilage Tissue Engineering

Studies of the Lumbar Vertebral End-plate Region in the Pig

Cited2 modulates hypoxia‐inducible factor–dependent expression of vascular endothelial growth factor in nucleus pulposus cells of the rat intervertebral disc

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