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J Menage

Publications and source records attributed to J Menage.

At least 19 recordsLinked to original sources
PubMed2004

TNFalpha-stimulated gene product (TSG-6) and its binding protein, IalphaI, in the human intervertebral disc: new molecules for the disc.

Inflammation and irritation of the nerve roots has been indicated as an important factor in the pain associated with symptomatic disc herniations. Tumour necrosis factor alpha (TNFalpha) is now believed to be involved in this pathway. TNFalpha causes connective tissue cells in culture to synthesise a glycoprotein, TNFalpha-stimulated gene-6 (TSG-6). TSG-6 is found in inflammatory diseases of related connective tissues, such as articular cartilage in rheumatoid arthritis, but is not present in unaffected individuals. In order to determine if TSG-6 occurred in intervertebral disc (and cartilage endplate), we have investigated the presence of TSG-6 and its binding protein, inter-alpha-inhibitor (IalphaI), in 58 herniated and 15 non-herniated discs. Immunostaining for the cytokines, IL-1alpha, IL-1beta and TNFalpha, has also been carried out. We have demonstrated that both TSG-6 and IalphaI occur commonly in human intervertebral disc matrix with at least some TSG-6 in 98% of discs studied and IalphaI in all of them. Staining for TSG-6 was greatest in herniated discs, particularly close to blood vessels. IalphaI immunostaining was frequently widespread throughout the disc but there was little in the cartilage endplate. It has been proposed that these molecules have widespread effects, including extracellular matrix stabilisation, down-regulation of the protease network and reduction of inflammation. Hence, the occurrence of TSG-6 and IalphaI in disc tissue could have implications in the aetiopathogenesis and future therapeutics of intervertebral disc disease.

Adolescent↗
PubMed2001

Immunohistochemical detection of Schwann cells in innervated and vascularized human intervertebral discs.

STUDY DESIGN: The ingrowth of nerves, blood vessels, and Schwann cells into human intervertebral discs was examined using immunohistochemistry for cell-type-specific markers. OBJECTIVES: To determine whether Schwann cells may contribute to disc innervation, and to assess the relation between disc innervation and vascularization. SUMMARY OF BACKGROUND DATA: Intervertebral disc degeneration was associated previously with ingrowth of blood vessels and nerves. Schwann cells are known to play an important role in regulating nerve growth and survival in other tissues, but they have not been examined in human pathologic intervertebral discs. METHODS: Serial sections of human intervertebral discs were immunostained for the neuronal markers (neurofilament 200, peripherin, protein gene product 9.5), for the Schwann cell marker (glial fibrillary acidic protein), and for the endothelial cell marker (CD34). RESULTS: Glial fibrillary acidic protein-immunopositive cells colocalized with nerves in degenerate discs, but were absent or rarely observed in nondegenerate, aneural discs. These also were seen in the disc matrix, independently of nerves. Much of the nerve and Schwann cell ingrowth was found in vascularized areas of disc tissue, where the lamellar structure of the anulus fibrosus was disrupted. Blood vessels were observed deeper into the discs than nerves or Schwann cells. CONCLUSIONS: The appearance of glial fibrillary acidic protein-immunopositive cells in diseased intervertebral discs was closely associated with nerve ingrowth. This novel finding suggests that Schwann cells have a role to play in regulating disc innervation and nerve function in the disc. Because blood vessels were observed furthermost into the disc, it is possible that degenerate disc vascularization occurs before innervation.

Adolescent↗
PubMed2001

Matrix turnover in human cartilage repair tissue in autologous chondrocyte implantation.

OBJECTIVE: Autologous chondrocyte implantation (ACI) is a form of tissue engineering that is being used increasingly to treat damaged articular cartilage. What happens at the graft site subsequent to the transplantation of chondrocytes beneath a periosteal flap has largely remained a matter of conjecture. We examined biopsy samples from the graft site using a panel of specific antibodies to investigate the cellular mechanisms involved and to determine whether remodeling of the matrix occurs. METHODS: Ten full-depth core biopsy samples were obtained from patients who had undergone ACI 9-30 months previously (ages 28-53 years), in addition to 6 "control" biopsy samples. Cryosections were evaluated by standard histologic examination using polarized light and immunohistochemistry. Antibodies specific for type II collagen (CIIC1) were used, as well as antibodies against the C-propeptide of type II collagen (R160) and its denaturation product (Col2-3/4m), as indicators of anabolism or catabolism. In addition, antibodies to the matrix proteinase-generated neoepitopes of the aggrecan core protein were used to demonstrate either aggrecanase (BC-3 and BC-13) or matrix metalloproteinase (MMP) (BC-4 and BC-14) activity. RESULTS: All biopsy samples stained for type II collagen, even in areas of fibrocartilaginous morphology. There was evidence of newly synthesized type II collagen in addition to denatured collagen. MMP and aggrecanase activity on the proteoglycan population was evident, with aggrecanase being more active in fibrocartilaginous areas. CONCLUSION: The findings of this study indicate that ACI is capable of not only cartilage repair but, in some cases, regeneration. This may be achieved by the turnover and remodeling of an initial fibrocartilaginous matrix via enzymatic degradation and synthesis of newly formed type II collagen.

Adolescent↗
PubMed2000

Matrix metalloproteinases and aggrecanase: their role in disorders of the human intervertebral disc.

STUDY DESIGN: A comprehensive immunohistochemical study of matrix metalloproteinase activity in discs from patients with different disc diseases. OBJECTIVES: To identify individual matrix metalloproteinase enzymes that could contribute to the degeneration of the matrix of the intervertebral disc, to identify the cells that produce matrix metalloproteinases (for example, the endogenous disc cells or invading cells associated with vascularisation), and to determine if "aggrecanase" contributes to degradation of proteoglycans in disc disorders. SUMMARY OF BACKGROUND DATA: Matrix disorganization and loss of substance are the most common findings in degenerate discs, and proteinase enzyme activity is one means of causing these changes. METHODS: Forty-nine discs from 46 patients with degenerative disc disease, posterior anular tears, spondylolisthesis, or disc herniation were studied immunohistochemically to determine the presence of matrix metalloproteinases 1, 2, 3, 7, 8, 9 and 13, tissue metalloproteinases 1 and 2, and proteoglycan degradation products generated by either matrix metalloproteinases or aggrecanase activity. In addition, in situ zymography was used to confirm matrix metalloproteinase activity. RESULTS: The most extensive staining was seen for matrix metalloproteinases 1, 2, 3, and 9, with 91%, 71%, 65%, and 72% of samples having some immunopositivity for the respective antibodies. In contrast, staining for matrix metalloproteinases 7 and 8 was much less (38% for both). Tissue inhibitor of metalloproteinases 1 and 2 were expressed in 34% and 79% of specimens, respectively. Matrix metalloproteinases were found particularly in cell clusters and blood vessels of degenerate discs, with staining correlating positively with macroscopic degenerative grade. For all of the enzymes, there was most staining in the herniation specimens and least in the autopsy samples. The opposite was true of staining for the matrix metalloproteinases inhibitor, tissue inhibitor of metalloproteinases 2, with most found in the autopsy specimens. Enzyme activity was confirmed by in situ zymography and staining for matrix metalloproteinase degradation products of proteoglycans. In addition, there was staining with antibodies demonstrating aggrecanase degradation products. CONCLUSIONS: Matrix metalloproteinase activity is more prevalent in herniated discs than in other disc disorders studied, although matrix metalloproteinases may have been more common earlier in the disease progression. Matrix metalloproteinases can be produced by invading blood vessels and associated cells, as well as by indigenous disc cells. Aggrecanase activity, although present in some samples, was not as obvious as that of matrix metalloproteinases. In addition to altered matrix metalloproteinase production, there appears to be a change in the balance between enzymes and endogenous inhibitors, tissue inhibitors of metalloproteinases. This study highlights specific matrix metalloproteinases that might be most efficient to target in developing therapeutics for minimizing degradation of the extracellular matrix of the disc.

Adolescent↗
PubMed1998

Changes in collagen cross-linking in degenerative disc disease and scoliosis.

STUDY DESIGN: Biochemical study of the changes in the collagen cross-link profile of human intervertebral discs collected at surgery from patients with either low back pain associated with disc degeneration or scoliosis. OBJECTIVE: To determine whether changes occur in the collagen cross-link profile in the disc of patients with either low back pain associated with disc degeneration or scoliosis, which may well influence matrix integrity. Such changes in the cross-link profile of a tissue indicates increased matrix turnover and tissue remodeling and may have implications for the progression of these disorders. SUMMARY OF BACKGROUND DATA: The diseases of the intervertebral disc, degenerative disc disease and scoliosis, are both characterized by changes in the extracellular matrix components that will affect the mechanical function of the tissue. The stability of the collagenous components and hence the mechanical integrity of connective tissues such as the disc is dependent on the degree and type of cross-links between the collagen molecules. This article reports results on the distribution of the different cross-links in the disc and the changes that occur with age, degenerative disc disease, and scoliosis. METHODS: Thirty-three discs were obtained from patients with degenerative disc disease and 29 discs from patients with scoliosis. Samples were acid hydrolyzed and the collagen cross-links analyzed by either fractionation on an amino acid analyzer configured for cross-link analysis using ninhydrin postcolumn detection or fractionation by high-pressure liquid chromatography with fluorescence detection. RESULTS: The reducible cross-links and the mature cross-link all increased from the outer anulus fibrosus through into the nucleus pulposus. The highest levels of the mature cross-link were found in the cartilage end-plate. The nonenzymic derived cross-link, pentosidine, in contrast, showed little difference across the disc, but did show the expected age-related increase. In degenerative disc disease, no change in the levels of the reducible or mature cross-links was found, but a decrease was observed in the levels of the age-related cross-link pentosidine in the more severe disease samples. In scoliosis, significantly higher levels of the reducible cross-links were found on the convex than on the concave side of the scoliotic disc. CONCLUSIONS: These changes in the cross-link profile of the intervertebral disc in degenerative disc disease and scoliosis are indicative of increased matrix turnover and tissue remodeling and likely to have implications for the progression of these disorders.

Adolescent↗
PubMed1998

Type X collagen in the human invertebral disc: an indication of repair or remodelling?

The short-chained type X collagen was once thought to be produced exclusively by hypertrophic chondrocytes during endochondral ossification. More recently, however, it has been found elsewhere, for example in articular cartilage. In the present study, the occurrence of type X collagen in the intervertebral disc has been investigated. Human disc tissues of varying pathologies were examined for the presence of type X collagen and expression of alpha1(X) mRNA by immunohistochemistry and in situ hybridization respectively. All samples of disc contained areas that were immunoreactive but to varying extents. In the disc itself, staining for the protein and alpha1(X) mRNA was seen frequently associated with cells of the nucleus pulposus, which were large and of hypertrophic appearance, most commonly found in degenerate discs, and also in areas of disorganized architecture, such as clefts. In addition, type X collagen, both protein and mRNA, was found in regions of the cartilage end-plate, which calcify ectopically in scoliotic patients. We suggest that type X collagen production may be a response of disc tissue cells to a stimulus, such as altered loading.

Adolescent↗
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↗
PubMed1995

Mechanoreceptors in intervertebral discs. Morphology, distribution, and neuropeptides.

STUDY DESIGN: The present study investigated the occurrence and morphology of mechanoreceptors in human and bovine intervertebral discs and longitudinal ligaments. OBJECTIVE: To determine the type and frequency of mechanoreceptors present in intervertebral discs and anterior longitudinal ligaments in two patient groups, those with low back pain and those with scoliosis. Bovine coccygeal discs were examined. SUMMARY OF BACKGROUND DATA: Nerves have been described in intervertebral tissues, but there is little information on the endings of these nerves and their receptors, stimulation of which can cause a nerve impulse. METHODS: The presence of mechanoreceptors were investigated by immunolocalization of nerves and neuropeptides. By examining sequential sections, the frequency of receptors was assessed. RESULTS: Immunoreactivity to neural antigens showed mechanoreceptors in the anulus fibrosus and longitudinal ligaments of bovine and human specimens. Their morphology resembled Pacinian corpuscles, Ruffini endings, and, most frequently, Golgi tendon organs. They were found in 50% of discs investigated from patients with low back pain and in 15% of those with scoliosis. CONCLUSIONS: Mechanoreceptors were found in the outer 2-3 lamellae of the human intervertebral disc and anterior longitudinal ligament. Physiologic studies in other tissues indicate that these provide the individual with sensation of posture and movement, and in the case of Golgi tendon organs, of nociception. In addition to providing proprioception, mechanoreceptors are thought to have roles in maintaining muscle tone and reflexes. Their presence in the intervertebral disc and longitudinal ligament can have physiologic and clinical implications.

Adolescent↗
PubMed1994

Innervation of the spondylolysis "ligament".

SUMMARY OF BACKGROUND DATA: Spondylolysis of the lower lumbar vertebrae is a non-united childhood fracture of the arch of the vertebra, persisting into adult life. Symptoms of disabling low back pain appear in a minority of patients, usually for the first time in adulthood. This pain is considered to arise from several separate sources, one of which may be the spondylolysis ligament. STUDY DESIGN: The innervation of the ligament has been investigated immunohistochemically. METHODS: Specimens from eight patients were divided longitudinally for histology including hematoxylin and eosin, toluidine blue, and elastic van Gieson. Histochemistry involved immunostaining for the neuropeptides: protein gene product, calcitonin gene related peptide, substance P, vasoactive intestinal peptide, and the c-flanking peptide of neuropeptide Y. RESULTS: Immunoreactivity to calcitonin gene-related peptide, the c-peptide of neuropeptide Y, and vasoactive intestinal peptide was identified in the ligament or in the adjacent adipose tissue. CONCLUSION: The movement that the ligament allows at the fracture site may result in stimulation of the nerve endings both in the ligament and in the surrounding soft tissue.

Adult↗
PubMed1993

The cartilage end-plate and intervertebral disc in scoliosis: calcification and other sequelae.

The morphology and composition of the intervertebral disc and also of the cartilage end-plate were studied in patients with idiopathic or congenital scoliosis. The cartilage end-plate was investigated because of its function as an epiphyseal plate in humans and the association between growth and progression of the scoliotic curve. The proteoglycan and water contents were reduced in both structures in specimens from scoliotic patients, particularly toward the concavity of the curve, compared with autopsy material. The distribution of some collagen types differed in tissue from scoliotic patients and autopsy tissue. Calcification of the cartilage end-plate, and sometimes of the adjacent disc, occurred in all but three scoliotic patients, whereas there was minimal calcification in the autopsy specimens. We suggest that, although these changes are probably a secondary response to altered loading in the scoliotic patients, they may be highly significant to the progression of the scoliotic curve.

Adolescent↗
PubMed1992

The fluid content of the human intervertebral disc. Comparison between fluid content and swelling pressure profiles of discs removed at surgery and those taken postmortem.

The fluid content of the disc, which governs its mechanical response and biological behavior, varies with external load. Because load on the disc changes after death, the fluid content and swelling pressure profiles of human discs taken at autopsy were measured, and compared with discs removed during surgical procedures. In general, discs taken at surgery had a lower fluid content in the nucleus and a higher fluid content in the outer anulus than discs removed at autopsy. In discs removed at surgery, the swelling pressure of the nucleus was higher than that of the anulus, whereas in autopsy discs the swelling pressure profile was flat. These changes are though to result from changes in load after death, and could influence the results of in vitro mechanical tests on the disc.

Biomechanical Phenomena↗
PubMed1991

1991 Volvo Award in basic sciences. Collagen types around the cells of the intervertebral disc and cartilage end plate: an immunolocalization study.

Several types of collagen are known to exist in the intervertebral disc in addition to the fibrillar collagens, Types I and II. Although they constitute only a small percentage of the total collagen content, these minor collagens may have important functions. This study was designed to investigate the presence of Types I, II, III, IV, VI, and IX collagens in the intervertebral disc and cartilage end plate by immunohistochemistry, thereby establishing their location within the tissues. Types III and VI collagen have a pericellular distribution in animal and human tissue. No staining for Type IX collagen was present in normal human disc, but in rat and bovine intervertebral disc, it was also located pericellularly. These results show that cells of the intervertebral disc and cartilage end plate sit in fibrous capsules, forming chondrons similar to those described in articular cartilage. In pathologic tissue the amount and distribution of the collagen types, and the organization of the pericellular capsule, differ from that seen in control material.

Adult↗