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At least 19 recordsLinked to original sources

Requirements for an artificial intervertebral disc.

Intervertebral disc degeneration is an important social and economic problem. Presently available artificial intervertebral discs (AIDs) are insufficient and the main surgical intervention is still spinal fusion. The objective of the present study is to present a list of requirements for the development of an AID which could replace the human lumbar intervertebral disc and restore its function. The list addresses geometry, stiffness, range of motion, strength, facet joint function, center of rotation, fixation, failsafety and implantation technique. Date are obtained from the literature, quantified where possible and checked for consistency. Existing AIDs are evaluated according to the presented list of requirements. Endplate size is a weak point in existing AIDs. These should be large and fit vertebral bodies to prevent migration. Disc height and wedge angle should be restored, unless this would overstretch ligaments. Finally, stiffness and range of motion in all directions should equal those of the healthy disc, except for the axial rotation to relieve the facet joints.

Biomechanical Phenomena↗

Thermal analysis of the human intervertebral disc.

Intervertebral disc (IVD) degeneration is one of the most common musculuskeletal disorders affecting western society. Degeneration alters the morphology and the mechanical properties of the discs. According to previous reports, DSC proved to be a suitable method for the demonstration of thermal consequences of local as well as global conformational changes in the structure of the human intervertebral discs. In the present study, a wide spectrum of degenerated IVD was examined by DSC. The results suggest that definitive differences exist between the stages of disc degeneration in calorimetric measures.

Adolescent↗

Magnetic resonance imaging and spectroscopy of the intervertebral disc.

Intervertebral disc disease is an emerging health concern and has a considerable negative effect on the economy and on society. MRI has a critical role in assessing the disc, but it is still a challenge to objectively correlate disc health and pain with images. In this paper, a review of MR disc imaging techniques including grading, relaxation time measurements, diffusion, and contrast perfusion is presented. In addition, high-resolution magic-angle spinning methods to correlate in vitro disc degeneration (with pain, etc) are discussed. With the potential for gaining morphological and biochemical information, MRI shows promise for quantitative assessment of disc health.

Animals↗

[Ageing and degeneration of human lumbar intervertebral discs].

Intervertebral discs undergo serious age-related changes. It is generally accepted that degeneration of discs begins during the second decade of life, and it is well known that other structures of spine do not change as fast as the intervertebral discs. The most extensive degenerative changes occur in the nucleus pulposus, including degradation of proteoglycans aggregates with its fragmentation, dehydration, and loss of viable cells. Data available in literature, suggests that the most critical factor contributing to the degeneration, is increasing volume of the disc due to its growth, resulting in longer nutritional pathways and insufficient nutrition.

Age Factors↗

Osmoviscoelastic finite element model of the intervertebral disc.

Intervertebral discs have a primarily mechanical role in transmitting loads through the spine. The disc is subjected to a combination of elastic, viscous and osmotic forces; previous 3D models of the disc have typically neglected osmotic forces. The fibril-reinforced poroviscoelastic swelling model, which our group has recently developed, is used to compute the interplay of osmotic, viscous and elastic forces in an intervertebral disc under axial compressive load. The unloaded 3D finite element mesh equilibrates in a physiological solution, and exhibits an intradiscal pressure of about 0.2 MPa. Before and after axial loading the numerically simulated hydrostatic pressure compares well with the experimental ranges measured. Loading the disc decreased the height of the disc and results in an outward bulging of the outer annulus. Fiber stresses were highest on the most outward bulging on the posterior-lateral side. The osmotic forces resulted in tensile hoop stresses, which were higher than typical values in a non-osmotic disc. The computed axial stress profiles reproduced the main features of the stress profiles, in particular the characteristic posterior and anterior stress which were observed experimentally.

Cartilage↗

Senescence in human intervertebral discs.

Intervertebral discs demonstrate degenerative changes relatively early in life. Disc degeneration, in turn, is associated with back pain and disc herniation, both of which cause considerable clinical problems in the western world. Cell senescence has been linked to degenerative diseases of other connective tissues such as osteoarthritis. Thus we investigated the degree of cell senescence in different regions of discs from patients with different disc disorders. Discs were obtained from 25 patients with disc herniations; from 27 patients undergoing anterior surgery for either back pain due to degenerative disc disease (n = 25) or spondylolisthesis (n = 2) and from six patients with scoliosis. In addition, four discs were obtained post-mortem. Samples were classified as annulus fibrosus or nucleus pulposus and tissue sections were assessed for the degree of cell senescence (using the marker senescence-associated-beta-galactosidase (SA-beta-Gal)) and the number of cells present in clusters. There were significantly more SA-beta-Gal positive cells in herniated discs (8.5% of cells) than those with degenerative disc disease, spondylolisthesis, scoliosis, or cadaveric discs (0.5% of cells; P < 0.001). There was more senescence of cells of the nucleus pulposus compared to those of the annulus fibrosus and in herniated discs a higher proportion of cells in cell clusters (defined as groups of three or more cells) were SA-beta-Gal positive (25.5%) compared to cells not in clusters (4.2%, P < 0.0001). This study demonstrates an increased degree of cell senescence in herniated discs, particularly in the nucleus where cell clusters occur. These clusters have been shown previously to form via cell proliferation, which is likely to explain the increased senescence. These findings could have two important clinical implications: firstly, that since senescent cells are known to behave abnormally in other locations, they may lead to deleterious effects on the disc matrix and so contribute to the pathogenesis and secondly, cells from such tissue may not be ideal for cell therapy and repair via tissue engineering.

Adolescent↗

CD24 is expressed specifically in the nucleus pulposus of intervertebral discs.

Intervertebral disc (IVD) consists of a soft gelatinous material in its center, the nucleus pulposus (NP), bounded peripherally by fibrocartilage, annulus fibrosus (AF). Despite the number of patients with IVD degeneration, gene expression analysis has not been undertaken in NP and therefore little is known about the molecular markers expressed in NP. Here, we undertook a microarray screen in NP with the other nine tissues to identify the specific cell surface markers for NP. Five membrane associating molecules out of 10,490 genes were identified as highly expressing genes in NP compared with the other tissues. Among them, we identified CD24, a glycosylphosphatidylinositol (GPI) anchor protein as a cell surface marker for NP. CD24 expression was also detected in the herniated NP and chordoma, a malignant primary tumor derived from notochordal cells, while it was absent in chondrosarcoma. Therefore, CD24 is a molecular marker for NP as well as the diseases of IVD.

Animals↗

Uridine diphosphoglucose dehydrogenase in the intervertebral disc.

Intervertebral discs of an old sheep and a young pig were examined for the presence of cells containing the enzyme uridine diphosphoglucose dehydrogenase. In the sheep, the inner anulus had a higher proportion of active cells than the outer anulus; in the pig, there was no difference. From a consideration of cell numbers, it is suggested that there is an accumulation of glycosaminoglycans in the centre of the disc rather than an increased production rate. Notochordal cells in the pig disc contain uridine diphosphoglucose dehydrogenase and are capable of producing glycosaminoglycans.

Alcohol Oxidoreductases↗

Mechanobiology of the intervertebral disc.

Intervertebral disc degeneration has been linked in humans to extreme spinal loading regimens. However, mechanisms by which spinal force influences disc cellularity, morphology and consequently biomechanical function are unclear. To gain insight into mechanobiological interactions within the disc, we developed an in vivo murine tail-compression model. Results from this model demonstrate how deviations in spinal stress induce a cycle of altered cell function and morphology as the disc remodels to a new homoeostatic configuration.

Aging↗

Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc.

Intervertebral disc (IVD) degeneration, a common cause of low back pain in humans, is a relentlessly progressive phenomenon with no currently available effective treatment. In an attempt to solve this dilemma, we transplanted autologous mesenchymal stem cells (MSCs) from bone marrow into a rabbit model of disc degeneration to determine if stem cells could repair degenerated IVDs. LacZ expressing MSCs were transplanted to rabbit L2-L3, L3-L4 and L4-L5 IVDs 2 weeks after induction of degeneration. Changes in disc height by plain radiograph, T2-weighted signal intensity in magnetic resonance imaging (MRI), histology, immunohistochemistry and matrix associated gene expressions were evaluated between normal controls (NC) without operations, sham operated with only disc degeneration being induced, and MSC-transplanted animals for a 24-week period. Results showed that after 24 weeks post-MSC transplantation, degenerated discs of MSC-transplanted group animals regained a disc height value of about 91%, MRI signal intensity of about 81%, compared to NC group discs. On the other hand, sham-operated group discs demonstrated the disc height value of about 67% and MRI signal intensity of about 60%. Macroscopic and histological evaluations confirmed relatively preserved nucleus with circular annulus structure in MSC-transplanted discs compared to indistinct structure seen in sham. Restoration of proteoglycan accumulation in MSC-transplanted discs was suggested from immunohistochemistry and gene expression analysis. These data indicate that transplantation of MSCs effectively led to regeneration of IVDs in a rabbit model of disc degeneration as suggested in our previous pilot study. MSCs may serve as a valuable resource in cell transplantation therapy for degenerative disc disease.

Aggrecans↗

Slow deformation of intervertebral discs.

Intervertebral discs exhibit pronounced time-dependent deformations when subjected to load variations. These deformations are caused by fluid flow to and from the disc and by viscoelastic deformation of annulus fibres. The fluid flow is caused by differences between mechanical and osmotic pressure. A mechanical model of lumbar disc functions allows one to calculate both the extent of fluid flow and its implications for disc height as well as the role played by viscoelastic deformation of annulus fibres. From such calculations changes in body height are estimated. Experimental results already documented in the literature offer bases for the determination of the parameters involved. Body height variations are studied, both those related to normal diurnal rhythmicity and those related to somewhat exceptional circumstances. The normal diurnal fluid flow is found to be about +/- 40% of the disc fluid content late in the evening. Viscoelastic deformation of annulus fibres contributes approximately one quarter of the height change obtained after several hours normal activity, but dominates during the first hour.

Adult↗

Collagen stability and cross-linking in normal and kyphoscoliotic mouse intervertebral discs.

Intervertebral discs of the cervical-thoracic region of the spine of BDL mice which are homozygous for the ky gene mutation undergo degeneration. Discs from these mice have a normal collagen content and undergo normal collagen cross linking prior to the appearance of degenerative changes. The major reducible collagen cross-link formed in discs of these mice and in normal CBA strain mice is hydroxylysino-5-ketonorleucine. These results and other previous results indicate that the discs in the ky mouse develop degenerative disease due to an extrinsic factor rather than to an intrinsic abnormality of their extracellular matrix. The extrinsic factor has been identified as spinal muscle atrophy.

Animals↗

Extracellular matrix in development of the intervertebral disc.

Intervertebral discs allow bending and twisting of the spine whilst resisting compression from gravity and muscle action, and are composite structures of the peripheral annulus fibrosus enclosing the nucleus pulposus. Their development is complex, involving several different connective tissue types, yet little is known of the developing extracellular matrix (ECM). We report the ECM composition of foetal rat discs from their first appearance to birth. The earliest collagen detected was type III, which was subsequently replaced by type II in the cartilaginous inner annulus and joined by type I in the fibrous outer annulus. Type IV collagen appeared in outer annulus, associated with myofibroblast-like cells of the orienting collagenous lamellae. Laminin and fibronectin co-distributed here in later stages, although overall they had a wider distribution. Aggrecan occurred in early nucleus pulposus and then appeared in the inner annulus, in association with cartilage differentiation. Versican appeared later in the inner annulus, and also in the dorsal region of the outer annulus. Comparisons of glycosaminoglycan and proteoglycan label allowed extrapolations to be made as to likely glycosaminoglycan components of the large proteoglycans, and of other proteoglycans that may be present - thus differential distribution of aggrecan and keratan sulfate label suggested the presence of fibromodulin and/or lumican. Functionally aggrecan would confer compression resistance to cartilaginous structures. Versican may also contribute, but along with the small proteoglycans is likely to be associated with various stages of control of cell differentiation, tissue morphogenesis and collagen fibre formation in the assembly of the annulus fibrosus.

Animals↗

Effect of AGEs on human disc herniation: intervertebral disc hernia is also effected by AGEs.

Currently, extracellular matrix MMP has been discussed in relation to the extrusion and spontaneous regression of the herniated mass observed in lumbar disc herniation. However, the question remains as to whether degenerated protein is really the cause of this condition's pathogenesis. We confirmed immunologically by means of electron microscopy that extrusion is caused by the AGEs (advanced glycation end products)-induced cross-linking of collagen, and that spontaneous regression is due to AGE receptors on macrophages. Further, AGEs were found to be already exposed during histogenesis, suggesting a relation to apoptosis. In lumbar disc herniation and aging, glucose-derived AGEs cross-link proteins and cause vascular tissue damage.

Base Sequence↗

Amyloid in intervertebral discs. A histopathological investigation of intervertebral discs from 30 randomly selected autopsies.

Material from intervertebral discs obtained from 30 randomly selected autopsies was examined histologically for amyloid deposits. Various degrees of amyloid degeneration were found in the disc tissue from 28 of the autopsies. In the annulus fibrosus, the amyloid was lying between the thick bundles of collagen fibers, compared to a more diffuse nodular distribution in the nucleus pulposus, frequently in close relation to chondrocytes. With regard to the lumbar discs, a significant correlation was found between the occurrence of islands of chondroid tissue in the annulus fibrosus and amyloid degeneration. Significantly more amyloid was observed in disc tissue in older age groups, while the amount of amyloid was similar in discs from men and women. Calcium-pyrophosphate-dihydrate (pyrophosphate) was found in the tissue of 6 of the 7 women over the age of 70. Calcium phosphate was seen in 22 of the autopsies--more frequently in the annulus fibrosus than in the nucleus pulposus. There was no topographical relationship between calcium phosphate and amyloid.

Adult↗

Structural variation of the anterior and posterior anulus fibrosus in the development of human lumbar intervertebral disc. A risk factor for intervertebral disc rupture.

A morphologic comparison of the laminated structure of the anterior and posterior anulus fibrosus of lumbar intervertebral disc was made on 24 L3-4 and L4-5 discs obtained from 10 fetus, one child, and one young adult cadavers. Low power microscopic and polarized microscopic observations and measurements on the transverse sections were performed to assess 1) lamellar bundle arrangement, 2) number of distinct lamellar bundles, 3) percentage of incomplete lamellar bundles, and 4) fiber-interlacing angles. The number of lamellar bundles was greater in the anterior anulus than in the posterior anulus. A very complex structure was observed in the posterior middle anulus in all the specimens, with a high percentage of incomplete/discontinuous lamellar bundles and greater fiber-interlacing angles. Loose connection of the lamellar bundles of posterior outer anulus was observed in fetal discs. The annular strength was not measured in the present study, however, the risk of posterior disc rupture in the young may be influenced by an inherent structural variation with a weak posterior anulus fibrosus.

Adult↗