Nutrition of the Intervertebral Disc

Urban, Jill; Holm, Sture; MAROUDAS, A.; Nachemson, Alf

doi:10.1097/00003086-198210000-00039

Cited by 757 publications

(169 citation statements)

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“…However, it is unlikely that changes in the nervous and cardiovascular systems give rise to ectopic mineralization in ENT1 -/-mice, especially of the inner annulus fibrosus, which is considered an avascular and aneural tissue. (46,47) In the present study, we found that plasma adenosine concentrations are significantly elevated in the ENT1 -/-mice compared to wild-type littermates, as reported previously. (41) The greater plasma concentration of adenosine in ENT1 -/-mice likely reflects extracellular accumulation of adenosine due to lack of uptake by cells that normally express ENT1, one of the primary uptake pathways for adenosine.…”

Section: Discussionsupporting

confidence: 91%

Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans

Warraich

Bone

Quinonez

et al. 2012

Journal of Bone and Mineral Research

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Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy, characterized by ectopic calcification of spinal tissues. Symptoms include spine pain and stiffness, and in severe cases dysphagia and spinal cord compression. The etiology of DISH is unknown and there are no specific treatments. Recent studies have suggested a role for purine metabolism in the regulation of biomineralization. Equilibrative nucleoside transporter 1 (ENT1) transfers hydrophilic nucleosides, such as adenosine, across the plasma membrane. In mice lacking ENT1, we observed the development of calcified lesions resembling DISH. By 12 months of age, ENT1 -/-mice exhibited signs of spine stiffness, hind limb dysfunction, and paralysis. Micro-computed tomography (mCT) revealed ectopic mineralization of paraspinal tissues in the cervical-thoracic region at 2 months of age, which extended to the lumbar and caudal regions with advancing age. Energy-dispersive X-ray microanalysis of lesions revealed a high content of calcium and phosphorus with a ratio similar to that of cortical bone. At 12 months of age, histological examination of ENT1 -/-mice revealed large, irregular accumulations of eosinophilic material in paraspinal ligaments and entheses, intervertebral discs, and sternocostal articulations. There was no evidence of mineralization in appendicular joints or blood vessels, indicating specificity for the axial skeleton. Plasma adenosine levels were significantly greater in ENT1 -/-mice than in wild-type, consistent with loss of ENT1-a primary adenosine uptake pathway. There was a significant reduction in the expression of Enpp1, Ank, and Alpl in intervertebral discs from ENT1 -/-mice compared to wild-type mice. Elevated plasma levels of inorganic pyrophosphate in ENT1 -/-mice indicated generalized disruption of pyrophosphate homeostasis. This is the first report of a role for ENT1 in regulating the calcification of soft tissues. Moreover, ENT1 -/-mice may be a useful model for investigating pathogenesis and evaluating therapeutics for the prevention of mineralization in DISH and related disorders. ß

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Section: Discussionsupporting

confidence: 91%

Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans

Warraich

Bone

Quinonez

et al. 2012

Journal of Bone and Mineral Research

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“…Cell density in the intervertebral disc starts to decrease during childhood [68]. The loss of cellularity leads to a decrease and fragmentation of the proteoglycan content [13], especially in the nucleus, and to a reduction of matrix turnover which, in turn, induces cross-linking of collagen fibrils that reduces the self-repairing capability of the disc [16,59].…”

Section: Cellular and Matrix Changesmentioning

confidence: 99%

Ageing and degenerative changes of the intervertebral disc and their impact on spinal flexibility

et al. 2014

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Purpose Degeneration of the intervertebral disc is associated with various morphological changes of the disc itself and of the adjacent structures, such as reduction of the water content, collapse of the intervertebral space, disruption and tears, and osteophytes. These morphological changes of the disc are linked to alterations of the spine flexibility. This paper aims to review the literature about the ageing and degenerative changes of the intervertebral disc and their link with alterations in spinal biomechanics, with emphasis on flexibility. Methods Narrative literature review. Results Clinical instability of the motion segment, usually related to increased flexibility and hypothesized to be connected to early, mild disc degeneration and believed to be responsible for low back pain, was tested in numerous in vitro studies. Despite some disagreement in the findings, a trend toward spinal stiffening with the increasing degeneration was observed in most studies. Tests about tears and fissures showed inconsistent results, as well as for disc collapse and dehydration. Vertebral osteophytes were found to be effective in stabilizing the spine in bending motions. Conclusions The literature suggests that the degenerative changes of the intervertebral disc and surrounding structures lead to subtle alteration of the mechanical properties of the functional spinal unit. A trend toward spinal stiffening with the increasing degeneration has been observed in most studies.

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“…Moreover, rare glycogen deposits were seen in the control specimens presenting a low radiological degeneration grade in the aged control group. On the other hand, it is known that EP sclerosis causes a decrease in nutrient supply and, thus, advanced changes in the IVD [7,26,47]. Only half of the control discs, but nearly all of the herniated discs showed an in-growth of vascular vessels from the longitudinal ligament inwards the outer AF.…”

Section: Discussionmentioning

confidence: 97%

“…Roberts et al published that changes seen with ageing are similar to those seen in degenerative disc disease and that this cause discussion as to whether ageing and degeneration are same processes or have to be separated [6]. As the largest avascular tissue, the healthy mature discs contains only limited blood vessels and nerves in the outer AF and is mainly dependent on the nutrient supply through the endplate by diffusion [7,26]. Horner et al stated that because the extracellular matrix is synthesized and maintained by the cells of the disc, the profiles of extracellular matrix composition across the disc presumably arise from differences in cellular activity.…”

Section: Discussionmentioning

confidence: 99%

Morphological changes in disc herniation in the lower cervical spine: an ultrastructural study

Sitte

Kathrein²,

Pedross

et al. 2012

Eur Spine J

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Nutrition of the Intervertebral Disc

Cited by 757 publications

References 0 publications

Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans

Loss of equilibrative nucleoside transporter 1 in mice leads to progressive ectopic mineralization of spinal tissues resembling diffuse idiopathic skeletal hyperostosis in humans

Ageing and degenerative changes of the intervertebral disc and their impact on spinal flexibility

Morphological changes in disc herniation in the lower cervical spine: an ultrastructural study

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