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Static compression induces zonal-specific changes in gene expression for extracellular matrix and cytoskeletal proteins in intervertebral disc cells in vitro.

Compressive stimuli associated with weight-bearing and loading of the intervertebral disc are believed to be important regulators of disc cell metabolism. In this study, changes in gene expression levels for extracellular matrix and cytoskeletal proteins were quantified in disc cells in an alginate culture system subjected to static unconfined compression (25% compressive strain) after different time periods (2, 18 and 30 h). Differences in gene expression were observed between anulus fibrosus and nucleus pulposus cells following static compression for the matrix proteins studied here. Anulus fibrosus cells responded to mechanical deformation at the 30-h time point, with increasing gene expression for types I and II collagen, aggrecan, biglycan, decorin and lumican. In contrast, nucleus pulposus cells were not responsive to mechanical loading with changes in gene expression for these matrix proteins at any time. Our results also show that anulus fibrosus cells, but not nucleus pulposus cells, responded to static compression with increased expression of vimentin mRNA as well as increased polymerization of vimentin subunits. The results of the current study illustrate that fibrochondrocytes of the anulus fibrosus may regulate biosynthesis at the transcriptional level following mechanical deformation in an alginate construct. In contrast, the biological response of nucleus pulposus cells to these same stimuli is not detectable. These differences may be attributed to the presence of a notochordal cell population in the immature nucleus pulposus studied here, with a more diffuse and stiff cytoskeleton that may restrict deformations or shape changes upon compressive loading.

Animals↗

Immunohistological study of intervertebral disc herniation of lumbar spine.

In order to observe histological changes in the extruded and sequestrated intervertebral disc, we conducted pathological and immunological examinations of herniated disc materials taken at the time of discectomy. There were 49 disc materials (from 38 men and 10 women [aged 19 to 78 years; average, 36.6 years]). The herniation was classified into four types, based on the intraoperative observations: protrusion (P), subligamentous extrusion (SE), transligamentous extrusion (TE), and sequestration (S). There were 19 P type discs, 3 SE type, 10 TE type, and 17 S type. The surgical specimens were stained with hematoxylin-eosin, as well as immunohistological staining with the labelled streptavidin biotin method, using human T-cell, human B-cell, and human macrophage antibodies. Inflammatory-cell infiltration was observed at the border of the disc. These findings were present in 19 discs (70%) of the 27 discs of TE and S types (10 TE and 17 S types), but were not seen in the 22 discs of P and SE types (19 P and 3 SE types). Immunohistological staining of the area with inflammatory-cell infiltration revealed the presence of T cells and macrophages, which suggested that this cell infiltration originated from T cells and macrophages, and that the spontaneous resorption of the disc may have resulted from the phagocytic activities of these cells.

Adult↗

Urinary retention and intervertebral disc protrusion.

The case histories of 17 patients in whom urinary retention was associated with an intervertebral disc protrusion which occurred, most commonly, centrally at the lumbar 4/5 level are presented. Strong pleas are made for consideration of this entity in patients with unexplained urinary retention.

Adult↗

Development of a prosthetic intervertebral disc.

This article is a preliminary report of a 10-year investigation of the development of an intervertebral disc prosthesis. Spinal fusion is a method for the treatment of chronic, disabling low-back pain that does not respond to nonoperative treatments. Spinal fusion, however, has various adverse effects, and the results of spinal fusion are often unpredictable. The goal of this research project was to develop disc prostheses that have mechanical properties very similar to those of natural, normal discs. Two types of disc prosthesis, one with fiber-reinforced polyurethane and the other with multicomponent, non-fiber-reinforced polymers (C-Flex), have been designed and manufactured. The fiber-reinforced disc was made of polyurethane end-plates with A100 hardness, a homogenous nucleus with A40, and 12 layers of multidirectional (0, +45 degrees), fiber-reinforced anulus with A40 polyurethane. The design and modeling of the multicomponent polymers (non-fiber-reinforced) was made of C-Flex endplates with A90 hardness, a nucleus with A35 occupying 35% of the volume, and an anulus with 70A. Mechanical testing of these disc prostheses demonstrated similar mechanical properties to those of natural, normal discs.

Biocompatible Materials↗

The effect of posture on the fluid content of lumbar intervertebral discs.

Cadaveric lumbar motion segments were creep loaded for 4 hours, and the fluid content of the intervertebral discs was measured and compared with that of unloaded discs. Half of the specimens were wedged to simulate sitting with the lumbar spine flexed, and the other half were wedged to simulate sitting or standing erect. The results showed that "flexed" discs lost more fluid, especially from the nucleus pulposus, than did the "erect" discs. It is concluded that fluid flow in flexed postures can aid the nutrition of the lumbar discs.

Adult↗

Bulging of lumbar intervertebral discs: non-contacting measurements of anatomical specimens.

A noncontacting photogrammetric method was used to measure intervertebral disc bulge (deformation perpendicular to the disc surface) at an anterior site and a posterolateral site of 17 human lumbar discs. Specimens were tested in constructs consisting of two lumbar vertebrae and the intervening disc. The posterior elements were removed to give unobstructed visibility of the posterolateral aspects. Stereophotogrammetry was used to record the motion of target points attached to the disc and vertebral body surfaces. In axial loading, the bulging increased linearly with disc compression, which in turn had a nonlinear relationship with the applied load. Axial loads and offset compression loads of physiologic magnitude caused disc bulge that was generally less than 1 mm. Axial torsion of an otherwise unloaded specimen produced minimal change in disc bulge. The disc bulging measured in this study is generally less than that previously reported, especially for angular motions between the vertebrae. This is probably because the photogrammetric method used here is independent of motion of the vertebrae, which can corrupt mechanical, contacting methods of measurement.

Biomechanical Phenomena↗

Occupation and risk of herniated lumbar intervertebral disc or sciatica leading to hospitalization.

Various occupations were studied for the prediction of herniated lumbar intervertebral disc or sciatica in 592 men and women who had been discharged from hospital with these diagnoses during an 11-year follow-up after a health examination. The cases were compared with 2140 controls matched individually for sex, age and place of residence. Subjects who, at the initial examination before the follow-up, had reported a history of back pain or sciatica were excluded. In men, the risk of being hospitalized due to herniated lumbar disc or sciatica was lowest in professional and related occupations, significantly higher in all other groups and highest among blue-collar workers in industry and among motor vehicle drivers. The variation in the risk between occupational groups of women proved less but was nevertheless still apparent. However, in women, but not in men, the risk was significantly associated with self-assessed strenuousness of work.

Adult↗

Collagens in the injured porcine intervertebral disc.

Spinal pain often is thought to be due to degeneration and mechanical failure of the intervertebral disc. Since the mechanical strength of the tissue depends on collagen fibers, the present study was designed to investigate the reactions in collagen metabolism after an experimentally induced disc injury. Five domestic pigs underwent an incision in the anterior part of the annulus fibrosus of disc L4-L5 through a retroperitoneal approach. The animals were killed 3 months postoperatively, and the injured discs and intact discs (controls) from different animals were removed for chemical analysis. Slices were cut from seven different parts across the disc. The concentration of total collagen (hydroxyproline [Hyp]), the activities of the two key enzymes in collagen biosynthesis (prolyl 4-hydroxylase [PH] and galactosylhydroxylysyl glucosyltransferase [GGT]), and the concentration of mature collagen crosslinks (hydroxypyridinium [HP]) were determined. In all experimental discs, the morphology had changed considerably: the nucleus pulposus was small, fibrous, and yellowish. The annular lamellar structure was partially destroyed and had been replaced by granulation tissue in the region of the injury. Large osteophytes had formed at the ventral edges of the vertebral bodies. In the nucleus pulposus, the Hyp concentration and the activities of PH and GGT were significantly increased, whereas the water content had decreased. The concentration of HP crosslinks was decreased in the anterior annulus fibrosus.

Animals↗

'Stress' distributions inside intervertebral discs. The effects of age and degeneration.

We investigated the distribution of compressive 'stress' within cadaver intervertebral discs, using a pressure transducer mounted in a 1.3 mm diameter needle. The needle was pulled along the midsagittal diameter of a lumbar disc with the face of the transducer either vertical or horizontal while the disc was subjected to a constant compressive force. The resulting 'stress profiles' were analysed in order to characterise the distribution of vertical and horizontal compressive stress within each disc. A total of 87 discs from subjects aged between 16 and 87 years was examined. Our results showed that age-related degenerative changes reduced the diameter of the central hydrostatic region of each disc (the 'functional nucleus') by approximately 50%, and the pressure within this region fell by 30%. The width of the functional annulus increased by 80% and the height of compressive 'stress peaks' within it by 160%. The effects of age and degeneration were greater at L4/L5 than at L2/L3, and the posterior annulus was affected more than the anterior. Age and degeneration were themselves closely related, but the stage of degeneration had the greater effect on stress distributions. We suggest that structural changes within the annulus and endplate lead to a transfer of load from the nucleus to the posterior annulus. High 'stress' concentrations within the annulus may cause pain, and lead to further disruption.

Adolescent↗

Lysozyme, a major low-molecular-weight cationic protein of the intervertebral disc, which increases with ageing and degeneration.

Lysozyme was demonstrated to increase in content in the human intervertebral disc in a significant age-dependent manner. In young discs (less than 20 years) the levels were 440 U/g wet weight, whereas in older discs (greater than 65 years) the concentration was 3,460 U/g wet weight. These findings contrasted with the hexuronate level (as a marker of proteoglycans) and neutral sugar content of the tissues which decreased with age. The level of lysozyme determined in the disc tissue also correlated with the morphological grade of disc degeneration.

Adolescent↗