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Differential expression of proteoglycan epitopes by ovine intervertebral disc cells.

The alginate bead culture system has been utilised by several groups to examine the in vitro proteoglycan (PG) metabolism of chondrocytes and intervertebral disc cells, but the nature of the PGs produced has not been examined in detail. This is largely due to the difficulty of separating the anionically charged sodium alginate support matrix from PGs which are similarly charged. In the present study ovine annulus fibrosus, transitional zone and nucleus pulposus cells were dissociated enzymatically from their respective matrices by sequential digestion with pronase/clostridial collagenase and DNAase and then cultured in alginate beads for 10 d. The beads were solubilised and subjected to DEAE Sepharose CL6B anion exchange chromatography to separate the sodium alginate bead support matrix material quantitatively from the disc cell PGs. The alginate free bead PGs were then subjected to composite agarose polyacrylamide gel electrophoresis to resolve PG populations and the PGs were transferred to nitrocellulose membranes by semidry electroblotting. The PGs were identified by probing the blots with a panel of antibodies to defined PG core protein and glycosaminoglycan side chain epitopes. Alginate beads of disc cells were also embedded in paraffin wax and 4 microm sections cut to immunolocalise decorin, biglycan, versican, and the 7-D-4 PG epitope within the beads. Decorin and biglycan had similar distributions in the beads, being localised on the cell surface whereas versican and the 7-D-4 PG epitope were immunolocalised interterritoriarly. This study is the first to demonstrate that ovine disc cells synthesise versican in alginate bead culture. Furthermore the immunoblotting studies also showed that a proportion of the 7-D-4 PG epitope was colocalised with versican.

Alginates↗

Effects of Ge Gen Decoction on PGE2 content and COX activity in the degenarated cervical intervertebral discs of rats.

After the rat model of cervical spondylosis was developed for 6 months, the PGE2 content and COX activity in the cervical intervertebral discs were determined respectively by radioimmunoassay and catalytic activity assay. The results indicated that the PGE2 content and COX activity in the model rat increased significantly, and that Ge Gen Decoction could down-regulate the PGE2 content and inhibit COX activity. This is possibly one of the mechanisms of Ge Gen Decoction for treating cervical spondylosis.

Animals↗

Effects of mechanical loading on intervertebral disc metabolism in vivo.

The overall goal of this work is to define more clearly which mechanical loading conditions are associated with accelerated disc degeneration. This article briefly reviews recent studies describing the effects of mechanical loading on the metabolism of intervertebral disc cells and defines hypothetical models that provide a framework for quantitative relationships between mechanical loading and disc-cell metabolism. Disc cells respond to mechanical loading in a manner that depends on loading magnitude, frequency, and duration. On the basis of the current data, four models have been proposed to describe the effects of continuous loading on cellular metabolism: (1) on/off response, in which messenger ribonucleic acid (mRNA) transcription remains altered for the duration of loading; (2) maintenance, characterized by an initial change in mRNA levels with return to baseline levels; (3) adaptation, in which mRNA transcription is altered and remains at a new steady state; and (4) no response. In addition, five hypothetical mechanisms that describe the long-term consequences of these metabolic changes on disc-remodeling are presented. The transient nature of gene expression along with enzyme activation/inhibition is associated with changes at the protein level. The hypothetical models presented provide a framework for obtaining quantitative relationships between mechanical loading, gene expression, and changes at the compositional level; however, additional factors, such as regulatory mechanisms, must also be considered when describing disc-remodeling. A more quantitative relationship between mechanical loading effects and the metabolic response of the disc will contribute to injury prevention, facilitate more effective rehabilitation treatments, and help realize the potential of biologic and tissue engineering approaches toward disc repair.

Animals↗

Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs.

The notochord has major roles in vertebral column formation: indirectly by inducing sclerotome cell differentiation; and directly by forming the nucleus pulposus of intervertebral discs. Sox5 and Sox6 encode Sry-related HMG box transcription factors that act redundantly to promote chondroblast differentiation in all cartilages of the mouse embryo. We show that Sox5 and Sox6 are expressed in the notochord cell lineage and required for notochord late development. In Sox5(-/-)/Sox6(-/-) embryos, the notochord formed a typical rod-like structure. It fulfilled its inductive functions, as indicated by expression of sonic hedgehog and sclerotome specification. However, the notochord failed to become surrounded with an extracellular matrix sheath. This phenotype was associated with a downregulation of extracellular matrix genes, including the genes for collagen 2, aggrecan and perlecan in both notochord cells and surrounding chondrocytic cells of presumptive inner annuli and vertebral bodies. The mutant notochord then underwent an aberrant, fatal dismantling after sclerotome cell migration. Its cells became removed first from intervertebral spaces and then from vertebral bodies, and it progressively underwent apoptosis. Meanwhile, the development of inner annuli and vertebral bodies was dramatically impaired. Consequently, the vertebral column of Sox5(-/-)/Sox6(-/-) fetuses consisted of a very deficient cartilage and was devoid of nuclei pulposi. In Sox5(-/-)/Sox6(+/-) and more severely in Sox5(+/-)/Sox6(-/-) embryos, the notochord sheath was thinner, but cells survived. By birth, nuclei pulposi were rudimentary, and its cells poorly swelled and still expressing sonic hedgehog. Hence, Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and formation of nuclei pulposi. Through these roles and essential roles in cartilage formation, they are central transcriptional regulators of vertebral column development.

Animals↗

Diagnostic value of cervical somatosensory evoked potentials recorded from the intervertebral discs after median and ulnar nerve stimulation in cervical spondylotic myelopathy.

We have studied the cervical somatosensory evoked potentials (CSEPs) recorded referentially from serial intervertebral discs after stimulation of the median nerve or the ulnar nerve at the wrist in cervical spondylosis. In seven unilateral radiculopathies, the CSEPs evoked by stimulation on the asymptomatic side normally consisted of the P1-N1 and the P2-N2 components, which represented the potentials arising from the white matter and the gray matter, respectively. Of 21 myelopathies, the CSEPs revealed the white matter involvement with conduction block identified by abrupt P1-N1 amplitude reduction in 7, the gray matter involvement identified by P2-N2 amplitude reduction in 3, or a combination of both in 11. The CSEPs were useful not only for determining the level responsible for myelopathy but also for localizing the lesion in the transverse plane of the spinal cord.

Adult↗

Spinal cord swelling as a myelographic indicator of prognosis: a retrospective study in dogs with intervertebral disc disease and loss of deep pain perception.

The association of myelographic spinal cord swelling with neurological outcome was examined in 46 dogs with intervertebral disc disease and absence of deep pain perception (DPP). Spinal cord swelling was measured by calculating a ratio of the length of the loss of the myelographic dye column to the length of the second lumbar vertebra (L2). A positive neurological outcome was defined as return of voluntary motor function. A cut-off value for swelling:L2 of 5.0 was established by the creation of a receiver operator characteristic curve. Using a swelling:L2 ratio of 5.0 as a cutoff for indication of neurological recovery yielded a sensitivity of 74% and a specificity of 61%. Overall neurological recovery rate was 43%. Dogs with spinal cord swelling:L2 ratios less than 5.0 had a recovery rate of 61%, whereas dogs with a ratio greater than or equal to 5.0 had a recovery rate of 26%. Evaluation of these data by chi square analysis confirmed that a ratio less than 5.0 was associated with a positive outcome, and a ratio greater than or equal to 5.0 was associated with a negative outcome, (P < .05). Although other factors, such as duration of neurological signs, affect neurological outcome in dogs with no DPP, evaluation of myelographic spinal cord swelling can assist in establishing a prognosis.

Animals↗

Isolated intervertebral disc resorption. A source of mechanical and inflammatory back pain?

Seven patients underwent anterior interbody spinal fusions to alleviate pain due to resorption of an intervertebral disc. The anterior annulus of the discs at operation was inflamed. The specimens were studied histologically, and the findings are discussed. The demonstration of inflammation in the anterior annulus together with the recent identification of nerve fibres in the anterior annulus now allows a better understanding of discogenic pain and its management.

Adult↗

Does hyperextension have an unloading effect on the intervertebral disc?

A stadiometer (a device to measure the overall height of a subject) was used to determine the effect of hyperextension in rehydration of the intervertebral disc. Hyperextension for 20 minutes in a prone posture was compared with the prone posture alone for 20 minutes. The stadiometer measurement was made after the subject was exposed to 10 kg of loading applied to the shoulders for five minutes and after each of the recovery postures. It was found that hyperextension gave a significantly increased height recovery compared with the prone posture.

Adult↗

Effect of massotherapy on the in vivo free radical metabolism in patients with prolapse of lumbar intervertebral disc and cervical spondylopathy.

The endogenous free radical scavenger superoxide dismutase (SOD) and blood catalase (CAT) in 2 groups of patients with prolapse of lumbar intervertebral disc and cervical spondylopathy were lower than that of the healthy control group, while the -SH reflecting the metabolic disturbance of free radical was higher. After massotherapy, blood SOD and CAT were increased, while lipid peroxide (LPO), -SH in urine were decreased, demonstrating that there are distinct parallel relationships existing in the changes of these enzymes in blood and urine.

Adult↗

The herniated lumbar intervertebral disc in children and adolescents. Long-term follow-up of 101 cases treated by surgery.

The authors review 101 cases of herniated lumbar intervertebral disc in children and adolescents treated by surgery. The most significant etiologic and pathogenetic factors in this series were early onset of disc degeneration, congenital lumbosacral malformations, and repeated trauma. The main clinical symptom was pain, usually sciatica, while neurological symptoms were less common than they are in adults. In all patients diagnosed correctly with the aid of appropriate imaging studies (myelography, CT scan, MRI), discectomy by means of conservative hemilaminectomy achieved satisfactory results, except in two cases of concomitant spinal instability due to spondylolysis and in one case of recurrence.

Adolescent↗

Variation of the glycosaminoglycans of the intervertebral disc with ageing. II. Non-chondrodystrophoid breed.

The variation with age and spinal level of the glycosaminoglycan distribution in the greyhound (a non-chondrodystrophoid breed) intervertebral disc has been assessed by means of histochemical and chemical methods. The principal glycosaminoglycans of the greyhound disc are the chondroitin sulphates. With ageing, there is evidence of a decline in these components and the replacement by keratosulphate. The discs of this breed contain high proportions of sialic acid and hexosamines well into old age which are thought to be associated with non-collagenous proteins (glycoproteins). The maintenance of glycosaminoglycans and glycoprotein levels in the disc nucleus pulposus into old age is possibly associated with the relatively low incidence of disc disorders in the non-chondrodystrophoid breeds.

Aging↗

Chymopapain for herniated intervertebral disc. A methodologic analysis and an agenda for future research.

Chymopapain recently has won approval in the United States for use in chemonucleolysis of herniated intervertebral discs. New research findings will be emerging, but clinicians need criteria by which to assess new results, to evaluate the existing literature, and to strengthen future investigation. Twenty-six original articles on chemonucleolysis were reviewed according to nine criteria of validity and applicability. Common threats to validity were failure to use randomized controls, make blind outcome assessments, assure equal co-treatments, and to calculate statistical power when results were negative. Threats to applicability included wide variations and incomplete reporting of patient selection, procedure technique, and many relevant outcomes. Methods for improving these design features are suggested, and a basic study design is proposed for comparing chemonucleolysis with both surgical and conservative management techniques.

Chymopapain↗