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PubMed1995

Glycosaminoglycans in intervertebral disc amyloid deposits.

Intervertebral discs are a common site of localized articular and some forms of systemic articular amyloid deposition. Whether there is an intrinsic matrix factor that favours amyloid deposition in intervertebral disc connective tissues is uncertain, but it is known that small localized deposits of amyloid in intervertebral discs are largely age related. As the glycosaminoglycans (GAGs) composition of the intervertebral disc is known to change with age, and as some forms of systemic amyloid deposition have been shown to be associated with particular highly sulphated GAGs, we examined the GAGs profile of amyloid deposits in intervertebral discs using mucin histochemistry (Alcian blue: MgCl2 critical electrolyte concentration) and immunohistochemistry. We found strong staining for very highly sulphated GAGs (0.9 M and 1 M MgCl2) and confirmed the presence of keratan sulphate in both localized and systemic, dialysis-associated beta 2-microglobulin amyloid deposits within disc fibrocartilage. These findings suggest that qualitative and quantitative changes in matrix GAGs, particularly strongly sulphated GAGs such as keratan sulphate, may play a role in the pathogenesis of localized and systemic amyloid deposition in intervertebral discs.

Adolescent↗
PubMed2000

Cervical intervertebral disc space narrowing and size of intervertebral foramina.

Computer-assisted simulation of C4-C5, C5-C6, and C6-C7 intervertebral disc space narrowing was performed on 16 anatomic specimen cervical spines to determine the relationship of the cross sectional foraminal areas with the degree of narrowing of the cervical intervertebral disc space. Compared with normal foraminal area values, reduction of 20% to 30% of the foraminal area was found after 1 mm narrowing of the intervertebral disc spaces; reduction of 30% to 40% of the foraminal area was found after 2 mm narrowing of the intervertebral disc space; and reduction of 35% to 45% of the foraminal area was found after 3 mm narrowing of the intervertebral disc space. Statistically significant differences were found among the remaining cross sectional foraminal areas after different degrees of intervertebral disc space narrowing. Compression of the nerve root within the intervertebral foramina after the collapse of the intervertebral disc space cannot be ignored, and an appropriate surgical procedure to maintain the normal height of the disc space is essential. The size of the intervertebral foramen is related directly to the height of the intervertebral disc space. A 3-mm vertical reduction of the intervertebral disc space is associated more frequently with severe narrowing of the neuroforamen.

Aged↗
PubMed1979

Histochemical study of the human intervertebral disc.

The human intervertebral discs which were obtained by cadavers and anterior discectomy are investigated histochemically. Chondroitin-4S, chondroitin-6S, dermatan sulfate, hyaluronic acid and keratan sulfate were detected in the human intervertebral disc by various histochemical methods. pH2.5, pH1.1 toluidin blue metachromasia and 0.4M MgCl2 alcianophilia became weaker with increasing age, and the herniated disc were weaker than controlled discs in the same age group. Chondroitin-4S and chondroitin-6S were distributed throughout the discs. There was no clear localization of the various glycosaminoglycans in the human intervertebral disc, with the exception of keratan sulfate. There was no histologically and histochemically observable difference in the cervical and lumbar discs.

Adult↗
PubMed1979

Proteoglycans of the intervertebral disc. Absence of degradation during the isolation of proteoglycans from the intervertebral disc.

Proteoglycans extracted with 4M-guanidinium chloride from pig intervetebral discs, and purified by equilibrium density-gradient centrifugation in CsCl, were of smaller hydrodynamic size than those extracted and purified in the same way from the laryngeal cartilage of the same animal. Whether this difference in size arose from degradation during the extraction and purification of the proteoglycans of the disc was investigated. Purified proteoglycans labelled either in the chondroitin sulphate chains or in the core protein were obtained from laryngeal cartilage by short-term organ culture. These labelled proteoglycans were added at the beginning of the extraction of the disc proteoglycans, and labelled cartilage and unlabelled disc proteoglycans were isolated and purified together. There was no appreciable loss of radioactivity after density-gradient centrifugation nor decrease in hydrodynamic size of the labelled cartilage proteoglycans on chromatography on Sepharose 2B, when these were present during the extraction of disc proteoglycans. It is concluded that disc proteoglycans are intrinsically of smaller size than cartilage proteoglycans and this difference in size does not arise from degradation during the extraction.

Animals↗
PubMed1981

The nerve supply to the human lumbar intervertebral discs.

The lumbar intervertebral discs are supplied by a variety of nerves. The posterior aspects of the discs and the posterior longitudinal ligament are innervated by the sinuvertebral nerves. The posterolateral aspects of the discs receive branches from adjacent ventral primary rami and from the grey rami communicantes near their junction with the ventral primary rami. The lateral aspects of the discs receive other branches from the rami communicantes. Some rami communicantes cross intervertebral discs and are embedded in the connective tissue of the disc deep to the origin of psoas. Such paradiscal rami are likely to be another source of innervation to the discs. The anterior longitudinal ligament is innervated by recurrent branches of rami communicantes.

Humans↗
PubMed2000

Morphology of young and old cervical spine intervertebral disc tissues.

The intervertebral disc of the cervical spine undergoes degenerative changes during the aging process. Although many studies have reported the qualitative changes in the disc, methodology to quantify these changes is lacking. The present study was designed to quantify the geometrical variations of the nucleus pulposus, annulus fibrosus and uncovertebral joints. The age groups of specimens were classified as juvenile, adult and aged. Fresh intervertebral discs with adjacent vertebral bodies of the lower cervical spine of primates were isolated. The specimens were sectioned sequentially in a coronal plane. Sections were stained with Hematoxylin and Eosin, Verhoeff's, Safranin O, and Trichrome methods to distinguish the nucleus, annulus and uncovertebral joints. Histological images were examined using light microscopy and processed using a computer imaging program to trace the boundaries of the disc components. Dorsal-to-ventral depth and medial-to-lateral width of the nucleus pulposus, and its relative location to the annulus pulposus were also obtained. In the juvenile and adult discs, the nucleus appeared as a light opaque region with scattered notochordal cells with a clear distinction from the annulus region. In contrast, in the aged discs, the nucleus appeared as a dense region of amorphous, irregular collagen materials with less distinction from the annulus region. With the progression of aging, the dorsal-to-ventral depth of the nucleus decreased considerably compared to medial-to-lateral width. The uncovertebral joints were clear in the adult discs. The joints were less distinct in the aged discs and their size decreased. Quantification of three-dimensional geometrical variations will assist in better defining the disc tissue in the mathematical models.

Aging↗
PubMed1998

Correlation between bone mineral density and intervertebral disc degeneration.

STUDY DESIGN: Intervertebral disc area, disc bulge ratio, and bone mineral density were measured in 86 postmenopausal women and the data analyzed. OBJECTIVE: To examine quantitatively the correlation between intervertebral disc degeneration and bone mass. SUMMARY OF BACKGROUND DATA: In results of previous studies, an inverse correlation between osteoporosis and spondylosis has been reported. In these studies, only radiographic findings were used to evaluate spondylosis; changes in the intervertebral disc itself were not investigated. METHODS: To determine bone mass, total-body bone mineral density, lumbar bone mineral density, and age-matched control values of bone mineral density were measured by dual-energy X-ray absorptiometry in all cases. To evaluate intervertebral disc degeneration, disc area and disc bulge ratio (calculated by measuring the areas protruding from lines connecting the middle points of the anterior and posterior borders of the vertebral bodies) were obtained from four discs, using magnetic resonance images of the lumbar spine. The correlation between bone mass data and disc area data was analyzed. RESULTS: Bone mineral density showed a significant decrease with increasing age. Disc area and disc bulge ratio had no relation to age. There was a negative correlation between total-body bone mineral density, lumbar bone mineral density, and age-matched control values versus disc area, and a positive correlation between all bone mineral density data and the disc bulge ratio. CONCLUSIONS: According to the results of the analysis by disc morphology and bone mass, especially total body bone mineral density, bone mass has an inverse correlation to intervertebral disc degeneration--i.e., reduction and disc bulge--which is important when considering degenerative spinal diseases and osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Effect of a prosthetic disc nucleus on the mobility and disc height of the L4-5 intervertebral disc postnucleotomy.

OBJECT: Current procedures for treatment of degenerative disc disease may not restore flexibility or disc height to the intervertebral disc. Recently, a prosthetic device, intended to replace the degenerated nucleus pulposus, was developed. In this biomechanical in vitro test the authors study the effect of implanting a prosthetic nucleus in cadaveric lumbar intervertebral discs postnucleotomy and determine if the flexibility and disc height of the L4-5 motion segment is restored. METHODS: The prosthetic disc nucleus device consists of two hydrogel pellets, each enclosed in a woven polyethylene jacket. Six human cadaveric lumbar motion segments (obtained in individuals who, at the time of death, were a mean age of 56.7 years) were loaded with moments of +/- 7.5 Nm in flexion-extension, lateral bending, and axial rotation. The following states were investigated: intact, postnucleotomy, and after device implantation. Range of motion (ROM) and neutral zone (NZ) measurements were determined. Change in disc height from the intact state was measured after nucleotomy and device implantation, with and without a 200-N preload. CONCLUSIONS: Compared with the intact state (100%), the nucleotomy increased the ROM in flexion-extension to 118%, lateral bending to 112%, and axial rotation to 121%; once the device was implanted the ROM was reduced to 102%, 88%, and 90%, respectively. The NZ increased the ROM to 210%, lateral bending to 173%, and axial rotation to 107% after nucleotomy, and 146%, 149%, 44%, respectively, after device implantation. A 200-N preload reduced the intact and postnucleotomy disc heights by approximately 1 mm and 2 mm, respectively. The original intact disc height was restored after implantation of the device. The results of the cadaveric L4-5 flexibility testing indicate that the device can potentially restore ROM, NZ, and disc height to the denucleated segment.

Adult↗
PubMedDate not supplied

The effect of static in vivo bending on the murine intervertebral disc.

BACKGROUND CONTEXT: Intervertebral disc cell function in vitro has been linked to features of the local environment that can be related to deformation of the extracellular matrix. Epidemiologic data suggest that certain regimens of spinal loading accelerate disc degeneration in vivo. Yet, the direct association between disc cell function, spinal loading and ultimately tissue degeneration is poorly characterized. PURPOSE: To examine the relationships between tensile and compressive matrix strains, cell activity and annular degradation. STUDY DESIGN/SETTING: An in vivo study of the biologic, morphologic and biomechanical consequences of static bending applied to the murine intervertebral disc. SUBJECT SAMPLE: Twenty-five skeletally mature Swiss Webster mice (12-week-old males) were used in this study. OUTCOME MEASURES: Bending neutral zone, bending stiffness, yield point in bending, number of apoptotic cells, annular matrix organization, cell shape, aggrecan gene expression, and collagen II gene expression. METHODS: Mouse tail discs were loaded for 1 week in vivo with an external device that applied bending stresses. Mid-sagittal sections of the discs were analyzed for cell death, collagen II and aggrecan gene expression, and tissue organization. Biomechanical testing was also performed to measure the bending stiffness and strength. RESULTS: Forceful disc bending induced increased cell death, decreased aggrecan gene expression and decreased tissue organization preferentially on the concave side. By contrast, collagen II gene expression was symmetrically reduced. Asymmetric loading did not alter bending mechanical behavior of the discs. CONCLUSIONS: In this model, annular cell death was related to excessive matrix compression (as opposed to tension). Collagen II gene expression was most negatively influenced by the static nature of the loading (immobilization), rather than the specific state of stress (tension or compression).

Analysis of Variance↗
PubMed2004

Mechanisms for mechanical damage in the intervertebral disc annulus fibrosus.

Intervertebral disc degeneration results in disorganization of the laminate structure of the annulus that may arise from mechanical microfailure. Failure mechanisms in the annulus were investigated using composite lamination theory and other analyses to calculate stresses in annulus layers, interlaminar shear stress, and the region of stress concentration around a fiber break. Scanning electron microscopy (SEM) was used to evaluate failure patterns in the annulus and evaluate novel structural features of the disc tissue. Stress concentrations in the annulus due to an isolated fiber break were localized to approximately 5 microm away from the break, and only considered a likely cause of annulus fibrosus failure (i.e., radial tears in the annulus) under extreme loading conditions or when collagen damage occurs over a relatively large region. Interlaminar shear stresses were calculated to be relatively large, to increase with layer thickness (as reported with degeneration), and were considered to be associated with propagation of circumferential tears in the annulus. SEM analysis of intervertebral disc annulus fibrosus tissue demonstrated a clear laminate structure, delamination, matrix cracking, and fiber failure. Novel structural features noted with SEM also included the presence of small tubules that appear to run along the length of collagen fibers in the annulus and a distinct collagenous structure representative of a pericellular matrix in the nucleus region.

Animals↗
PubMed1997

Does the thickness of the vertebral subchondral bone reflect the composition of the intervertebral disc?

Degeneration of the intervertebral disc, seen radiologically as loss of disc height, is often associated with apparent remodelling in the adjacent vertebral body. In contrast, maintenance or apparent increase in disc height is a common finding in osteoporosis, suggesting the properties of the intervertebral disc may be dependent on those of the vertebral body or vice versa. We have investigated this relationship by measuring the radiological thickness of the subchondral bone and comparing it to the chemical composition of the adjacent disc. Sagittal slabs were sampled from lumbar spines obtained at autopsy and X-rayed microfocally. The thickness of the subchondral bone was measured and correlated with the composition of the adjacent intervertebral disc. Eighty-three cadaveric endplates were studied from individuals aged 17-85 years. There was regional variation in thickness of the subchondral bone, being greater adjacent to the annulus than the nucleus, and the endplates cranial to the disc were thicker than those caudal. There was a positive correlation between the thickness of the subchondral bone and the proteoglycan content of the adjacent disc, particularly in the region of the nucleus. A weaker correlation was seen here between water content and thickness, whilst there was no significant correlation at the annulus or between the bone thickness and collagen content. The positive relationship between the radiographic thickness of vertebral subchondral bone and the proteoglycan content of the adjacent disc seen in human cadaveric material could be due to the bone responding to a greater hydrostatic pressure being exerted by discs with higher proteoglycan content than by those with less proteoglycan present. It is suggested that while this is true in "normal" specimens, the relationship becomes altered in disease states, possibly because of changes to the nutritional pathway of the disc, with resultant endplate-bone remodelling affecting the flow of solutes to and from the intervertebral disc.

Adolescent↗
PubMed2004

Human intervertebral disc cell culture for disc disorders.

Repair of degenerated intervertebral discs by engineered tissue is a clinical challenge in spinal surgery. Prerequisites are cultivation of intervertebral disc cells and determination of their biologic properties. The influence of disc damage in different spinal disorders on the outcome of disc cell cultures has not been discussed previously. This study showed the feasibility of cultivation of cells from damaged human intervertebral discs and the dependence of cellular culture properties on the underlying disc disorder. Human intervertebral disc cells were isolated from disc tissue obtained during surgical procedures for scoliosis, osteochondrosis, and disc herniation. After proliferation in monolayer culture, cells were embedded in a mixed matrix composed of fibrin and hyaluronic acid. Deoxyribonucleic acid content, hydroxyproline content, and proteoglycan synthesis were determined on Days 7, 14, and 21. In a three-dimensional environment only cells obtained from scoliotic and osteochondrotic discs showed significant deoxyribonucleic acid and proteoglycan synthesis. However, hydroxyproline content increased only in cells from scoliotic discs. The results of this study show that the formation of extracellular matrix components under three-dimensional culture conditions is dependent on the nature of intervertebral disc damage of the tissue processed.

Biomarkers↗
PubMed2005

2004 Young Investigator Award Winner: vertebral endplate marrow contact channel occlusions and intervertebral disc degeneration.

STUDY DESIGN: Intervertebral disc degeneration was evaluated by morphologic appearance, magnetic resonance imaging, and by biochemical matrix composition. Caliber and distribution of openings of the adjacent vertebral osseous endplates were measured. OBJECTIVES: Correlation between occlusion of vertebral endplate openings and intervertebral disc degeneration was quantified. SUMMARY OF BACKGROUND DATA: Calcifications of vertebral endplates with disease and age have suggested insufficient nutrition as a mechanism for intervertebral disc degeneration. It has been proposed that occlusion of endplate openings, which contain vascular sources for the disc, may limit the transport of nutrients, leading to disc degeneration. METHODS: Fresh magnetic resonance images from 39 human lumbar discs were scored. Sectioned discs with endplates were morphologically graded. Samples of nuclear and anular regions were evaluated for proteoglycan and collagen contents. Backlight microscopic images of 4 endplate regions were obtained, and caliber and distribution of endplate openings for each disc were measured. Analysis of variance regression models were used to assess correlation between endplate openings and disc degeneration. RESULTS: The decrease in opening density significantly correlated to morphologic degeneration grade, best for openings with 20 to 50 im equivalent diameter and in the nuclear region. Although the density of 20 to 50 im openings also significantly indirectly correlated to age, it was not as strong as the correlation to degeneration grade. Opening density was also significantly correlated to proteoglycan content in all regions. However, all other biochemical parameters as well as the T2 intensity score showed only weak or no correlation to opening density. CONCLUSIONS: A high indirect correlation between the density of openings in the osseous endplate (particularly of the size of the capillary buds) and the morphologic degeneration grade of the disc support the hypothesis that occlusion of these openings may deprive the cells of nutrients, leading to insufficient maintenance of the extracellular matrix and disc degeneration.

Adult↗
PubMed2006

Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc.

Disc herniation treated by discectomy results in a significant loss of nucleus material and disc height. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. Chondrocytes that have been removed from damaged cartilaginous tissues maintain a capacity to proliferate, produce and secrete matrix components and respond to physical stimuli such as dynamic loading. Nucleus regeneration using autologous cultured disc-derived chondrocytes (ADCT) has been demonstrated in a canine model and in clinical pilot studies. In 2002 a prospective, controlled, randomised, multi-center study, EuroDISC, comparing safety and efficacy of autologous disc chondrocyte transplant, chondrotransplant DISC, plus discectomy (ADCT), with discectomy alone was initiated. A dog model was used to investigate the hypothesis that autologous disc chondrocytes can be used to repair damaged intervertebral disc. Disc chondrocytes were harvested and expanded in culture under controlled and defined conditions, returned to the same animals from which they had been sampled (autologous transplantation) via percutaneous delivery. The animals were analyzed at specific times after transplantation by several methods to examine whether disc chondrocytes integrated with the surrounding tissue, produced the appropriate intervertebral disc extracellular matrix, and might provide a formative solution to disc repair. The clinical goals of the EuroDISC study, were to provide long-term pain relief, maintain disc height and prevent adjacent segment disease. Interim analysis was performed after 2 years; Oswestry (low back pain/disability), Quebec Back-Pain Disability Scale, as well as Prolo and VAS score were used for the evaluation. Disc height was assessed by MRI. In the context of degenerative changes in an injury model: () autologous disc chondrocytes were expended in culture and returned to the disc by a minimally invasive procedure after 12 weeks; () disc chondrocytes remained viable after transplantation as shown by bromodeoxyuridine incorporation and maintained a capacity for proliferation after transplantation as depicted by histology; () transplanted disc chondrocytes produced an extracellular matrix that displayed composition similar to normal intervertebral disc tissue. Positive evidence of Proteoglycan content was supported by accepted histochemical staining techniques such as Safranin O-Fast Green; () both Type II and Type I collagens were demonstrated in the regenerated intervertebral disc matrix by immunohistochemistry after chondrocyte transplantation; and () when the disc heights were analyzed for variance according to treatment a statistically significant-correlation between transplanting cells and retention of disc height was achieved. A clinically significant reduction of low back pain in the ADCT-treated group was shown by all three pain score systems. The median total Oswestry score was 2 in the ADCT-treated group compared with 6 in the control group. Decreases in the disability index and VAS score in ADCT-treated patients correlated strongly with the reduction of low back pain. Decreases in disc height over time were only found in the control group, and of potential significance, intervertebral discs in adjacent segments appeared to retain hydration when compared to those adjacent to levels that had undergone discectomy without cell intervention. Autologous chondrocyte transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration.

Animals↗
PubMed2002

A comparative study of localization of heat shock protein 27 and heat shock protein 72 in the developmental and degenerative intervertebral discs.

STUDY DESIGN: The lumbar intervertebral discs of 135 subjects after autopsy were immunostained with antihuman heat shock protein 27 (HSP27) monoclonal antibody and antihuman heat shock protein 72 (HSP72) polyclonal antibody. OBJECTIVES: To present the data on metabolic changes that occurred in the chondrocytes of intervertebral discs during development and aging. SUMMARY OF BACKGROUND DATA: Heat shock proteins have been implicated in the progressive degeneration of articular cartilage in joint disease, such as rheumatoid arthritis and osteoarthritis. However, the role and expression of heat shock proteins in human intervertebral discs have received little study. METHODS: One hundred thirty-five specimens of human intervertebral discs were stained with hematoxylin and eosin, alcian blue, and Masson's trichrome and were immunostained with HSP27 and HSP72 by an indirect immunoperoxidase method. The relative amounts of HSP27 and HSP72 deposition were graded according to a semiquantitative scoring system. RESULTS: Heat shock protein 72 accumulated in the cytoplasm of the chondrocytes of both endplate cartilage and nucleus pulposus during gestation and thereafter decreased with aging (age, </=60 years), and HSP72 immunoreactivity increased in the chondrocytes of degenerative discs. In addition, HSP72 was located in the nuclei of certain chondrocytes of the degenerated nucleus pulposus and anulus fibrosus, was highly expressed in the chondrocytes of endplate cartilage during gestation and childhood, and thereafter decreased with aging. Furthermore, with the progressive degeneration of the endplate cartilage, HSP27 immunoreactivity increased. The degree of HSP27 immunoreactivity did not change significantly according to age in either the nucleus pulposus or the anulus fibrosus. CONCLUSIONS: Heat shock protein 27 and HSP72 are thus considered to be useful molecular indicators for degenerative change in intervertebral discs. Both HSP27 and HSP72 are presumed to play a role in cell protection from stress that is induced by mechanical and biologic factors causing intervertebral disc degeneration.

Adult↗
PubMed2006

Outcome and prognostic factors in non-ambulatory Hansen Type I intervertebral disc extrusions: 308 cases.

Thoracolumbar intervertebral disc disease is the most common cause of caudal paresis in dogs. Whilst the pathogenesis of the extrusion has been widely studied, treatment protocols and prognostic factors relating to outcome remain controversial. Recent studies have examined a multitude of factors relating to time to regain ambulation after decompressive surgery. Most intervertebral disc herniations occur in the thoracolumbar region, causing upper motor neuron signs in the rear limbs, which are thought to have a more favourable prognosis compared to the lower motor neuron signs created by herniation of an intervertebral disc in the caudal lumbar region. Due to the potential disruption of the lumbar intumescence, lower motor neuron signs have been reported as having a less favourable prognosis. The purpose of this study was to evaluate the intervertebral disc space as a prognostic factor relating to ambulatory outcome and time to ambulation after decompressive surgery. Hansen Type I intervertebral disc extrusions were studied in 308 non-ambulatory dogs. Preoperative and postoperative neurological status, corticosteroid use, signalment, intervertebral disc space, postoperative physical rehabilitation, previous hemilaminectomy surgery, disc fenestration, return to ambulation, and time to ambulation were reviewed.

Animals↗
PubMed1996

Immunohistochemical study of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 human intervertebral discs.

STUDY DESIGN: Immunohistologic staining of human intervertebral discs collected at the time of surgery (100 intervertebral discs from 80 patients) and 10 discs collected from 7 cadavers within 12 hours of death was performed using antimatrix metalloproteinase-3 monoclonal antibody and antitissue inhibitor of metalloproteinase-1 monoclonal antibody. OBJECTIVES: To examine the relationship between matrix destruction and staining for matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in intervertebral disc degeneration. SUMMARY OF BACKGROUND DATA: Matrix metalloproteinase-3, which decomposes aggregating proteoglycans, has attracted research attention as a substance contributing to matrix destruction in the articular cartilage and intervertebral disc. However, except for a few in vitro studies, the relationship between matrix destruction of the intervertebral disc and matrix metalloproteinase-3 has been little studied. METHODS: Immunohistologic staining was performed to examine the relationship between matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in the intervertebral disc, and the relationship of these two agents to magnetic resonance imaging, radiographic, and surgical findings. RESULTS: Those cases testing positive for matrix metalloproteinase-3 and negative for tissue inhibitor of metalloproteinase-1 accounted for most of the surgical specimens. The matrix metalloproteinase-3-positive cell ratio was significantly correlated with the magnetic resonance imaging grade of intervertebral disc degeneration, and the matrix metalloproteinase-3-positive cell ratio observed in prolapsed lumbar intervertebral discs was significantly higher than that in nonprolapsed discs. In cervical intervertebral discs, the matrix metalloproteinase-3-positive cell ratio and staining of cartilaginous endplate were correlated with the size of osteophyte formation. CONCLUSIONS: These findings suggested that intervertebral disc degeneration is caused by disturbance in the equilibrium of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1, and that matrix metalloproteinase-3 contributes to degeneration of the cartilaginous endplate.

Adolescent↗