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PubMed2006

Degree of degeneration and chondroitinase ABC treatment of human articular cartilage affect adhesion of chondrocytes.

The aim of the present study was to investigate whether degree of degeneration and chondroitinase ABC treatment of articular cartilage affect adhesion of chondrocytes to its surface. Human articular cartilage explants were harvested from patients undergoing total knee joint replacement arthroplasty, cut into discs of 0.5-0.8 mm thick and 3.75 mm in diameter, and then divided into three groups according to the degree of degeneration: G0, normal; G1, superficial fissures, and G2, deep fissures. These discs were stored at 70 degrees C until use. Chondrocytes (3 x 10(5) cell/mL in 100 microL of medium) isolated from articular cartilage by enzymatic digestion were transferred to a well plate containing cartilage discs and cultured for a maximum of 21 days. The cultures were divided into one of six groups according to the degree of degeneration and treatment of chondroitinase ABC of the disc. The morphologies of the disc surface and of cultured chondrocytes were assessed histologically. Chondrocyte adhesion, proliferation, and synthesis of proteoglycan and protein were analyzed. Chondrocyte adhesion significantly increased on the discs with higher degrees of degeneration, that is, maximum adhesion in G2, G1, and G0, subsequently. However, adhesion was not significantly different among the three groups at day 3. Chondrocyte adhesion on the chondroitinase ABC-treated disc significantly increased in comparison with that on the nontreated discs with the same degree of degeneration. However, proliferation of chondrocytes and synthesis of glycosaminoglycan and protein were not significant, regardless of degree of degeneration or chondroitinase ABC treatment. The present study demonstrated that chondrocyte adhesion on articular cartilage disc increased along with its degree of degeneration and with treatment of chondroitinase ABC, but that proliferation and synthesis of matrix of the cultured chondrocytes were not significantly influenced by both of them.

Aged↗
PubMed1995

Ubiquitin-positive degenerating neurites in the brainstem in Parkinson's disease.

Characteristic ubiquitin-positive, tau-negative, degenerating neurites were present in brainstem regions known to be involved in idiopathic Parkinson's disease. Corresponding changes were entirely absent from controls and from the brainstems obtained from patients who had died with Alzheimer's disease, motor neuron disease and multiple system atrophy. In Parkinson's disease cases degenerating neurites were particularly striking in the dorsal motor nucleus of the vagus. In this nucleus the density of degenerating neurites was inversely related to the duration of Parkinson's disease symptoms. Some ubiquitin-positive degenerating neurites also contained neurofilament immunoreactivity. However, confocal microscopy revealed that ubiquitin and neurofilament reactivities were located in separate regions of the degenerating neurite, suggesting that proteins other than neurofilaments may be important in the process of ubiquitination. The demonstration of ubiquitin-positive degenerating neurites in routinely prepared paraffin-embedded material, particularly in the dorsal motor nucleus of the vagus, could become diagnostically useful in those Parkinson's disease cases in which Lewy bodies are difficult to find. Demonstration of extensive ubiquitin-positive degenerating neurites might provide a clue to disease activity at the time of death.

Aged↗
PubMed1987

Identification of heritable spermatozoal degeneration within the ductus deferens of the chicken (Gallus domesticus).

Low-fertility (LF) roosters were identified within a line of Delaware chickens. However, LF could be overcome by frequent insemination. Electron microscopy revealed numerous degenerate spermatozoa in LF Delaware semen. Therefore, LF was attributed to suboptimal numbers of functional spermatozoa within the oviduct. Spermatozoal degeneration was not induced (p greater than 0.05) when Leghorn spermatozoa were incubated with Delaware seminal plasma. Ejaculates from F1 roosters were screened for spermatozoal degeneration via uptake of ethidium bromide. Roosters were categorized as producing few, 4 +/- 1% (mean +/- SEM), or numerous, 43 +/- 6%, degenerate spermatozoa. Only roosters within the latter group were characterized by LF (p less than 0.001). When such F1 and F2 roosters were ejaculated daily for 5 days, the percentage of degenerate spermatozoa decreased to less than or equal to 5%. Low fertility was not observed (p greater than 0.05) with such semen from F2 roosters. When these roosters had resumed ejaculating numerous degenerate spermatozoa after a period of sexual rest, 3 representative roosters were killed. Each ductus deferens was subdivided into 9 sections, and spermatozoal integrity was determined for semen from each section. Degeneration commenced in the mid-ductus deferens and progressively increased towards the receptaculum. Thus, a genetic defect resulting in a shortened functional life of the spermatozoon within the ductus deferens has been identified.

Animals↗
PubMed1992

Lumbar disc and back muscle degeneration on MRI: correlation to age and body mass.

Lumbar intervertebral discs and paraspinal muscles in 74 healthy volunteers ranging in age from 19 to 74 years were evaluated with MRI, and the occurrence of degeneration was correlated to age and body mass. Muscle size and the amount of fat in the muscles was studied from MRI cross sections. When the back muscles were degenerated, they were small and contained fat deposits. By contrast, the psoas muscles never showed gross fat deposits. Degeneration of both the lumbar discs and muscles increased with age. No correlation was found between muscle degeneration and overweight. Muscle degeneration is as common as disc degeneration in the lumbar area. MRI is an excellent method to assess both muscle and disc degeneration.

Adipose Tissue↗
PubMed1995

Distribution of the basic fibroblast growth factor and its receptor gene expression in normal and degenerated rat intervertebral discs.

STUDY DESIGN: Using a rat spondylosis model, the distributions of cells expressing the basic fibroblast growth factor and its receptor were investigated in normal and degenerated intervertebral discs. Cell-proliferating activity in degenerated discs was also assessed. OBJECTIVES: This study was conducted to determine whether basic fibroblast growth factor is related to intervertebral disc degeneration. SUMMARY OF BACKGROUND DATA: Basic fibroblast growth factor stimulates proliferation and matrix synthesis of cultured intervertebral disc cells. METHODS: Immunohistochemistry and in situ hybridization histochemistry were conducted to detect cells with basic fibroblast growth factor-like immunoreactivity and fibroblast growth factor receptor messenger RNA, respectively. Cell-proliferating activity was evaluated by AgNOR staining. RESULTS: In degenerated discs, round chondrocytes with basic fibroblast growth factor-like immunoreactivity and fibroblast growth factor receptor messenger RNA are scattered instead of spindle-shaped cells in the normal anulus (normal anular cells), which are devoid of basic fibroblast growth factor-like immunoreactivity and fibroblast growth factor receptor messenger RNA. The proliferating activity of these chondrocytes is suggested to exceed that of normal anular cells. CONCLUSION: Basic fibroblast growth factor is suggested to promote proliferation of chondrocytes in degenerated discs in an autocrine or paracrine manner. Basic fibroblast growth factor may be related to intervertebral disc degeneration as a proliferation-stimulating factor of chondrocytes that replace normal anular cells during disc degeneration.

Animals↗
PubMed1998

Disc degeneration and cervical instability. Correlation of magnetic resonance imaging with radiography.

STUDY DESIGN: An imaging study was designed to evaluate disc degeneration and segmental instability in the cervical spine. OBJECTIVES: To compare the magnetic resonance imaging assessment of disc degeneration with the conventional plain radiographic evaluation of cervical segmental instability. SUMMARY OF BACKGROUND DATA: No studies have been conducted to investigate the association of disc degeneration with cervical instability. METHODS: Two hundred sixty consecutive patients with suspected cervical spine disorders were analyzed for horizontal and angular displacements on lateral flexion and extension radiographs and disc degeneration on T2-weighted magnetic resonance images of the cervical vertebrae. RESULTS: In all intervertebral levels, the grade of disc degeneration increased significantly (P < 0.01) with age. Cervical instability was identified in 151 segments (14.5%) and correlated with Grade 1 and Grade 2 degeneration in the intervertebral discs (P < 0.01). CONCLUSIONS: Cervical segmental instability may indicate early degeneration of intervertebral disc in the cervical vertebrae.

Adult↗
PubMed1999

The anisotropic hydraulic permeability of human lumbar anulus fibrosus. Influence of age, degeneration, direction, and water content.

STUDY DESIGN: Experimental investigation to determine the effect of intervertebral disc degeneration on the kinetic behavior of fluid in human anulus fibrosus. OBJECTIVES: To measure the hydraulic permeability coefficient of anulus fibrosus specimens in the axial, circumferential, and radial directions to determine the anisotropic permeability behavior of nondegenerate and degenerate human intervertebral discs over a range of ages. SUMMARY OF BACKGROUND DATA: Fluid, a major component of normal intervertebral discs, plays a significant role in their load-supporting mechanisms. Transport of fluid through the intervertebral disc is important for cell nutrition and disc viscoelastic and swelling behaviors. The hydraulic permeability coefficient is the most important material property governing the rate of fluid transport. However, little is known about the anisotropic behavior of this kinetic property and how it is influenced by disc degeneration. METHODS: Using a permeation testing apparatus developed recently, testing was performed on 306 axial, circumferential, and radial anulus fibrosus specimens from the posterolateral region of 30 human lumbar (L2-L3) discs. A new method, flow-controlled testing protocol, was developed to measure the hydraulic permeability coefficient. RESULTS: The hydraulic permeability coefficient of anulus fibrosus depended significantly on the disc degenerative grade (P = 0.0001) and flow direction (P = 0.0001). For the nondegenerate group (Grade I), the hydraulic permeability was significantly anisotropic (P < 0.05), with the greatest value in the radial direction (1.924 x 10(-15) m4/Ns) and the lowest value in the circumferential direction (1.147 x 10(-15) m4/Ns). This anisotropic kinetic (flow) behavior of anulus fibrosus varied with disc degeneration. For the Grade III specimen group, there was no significant difference in hydraulic permeability coefficient among the three major directions (P = 0.37). With disc degeneration, the hydraulic permeability coefficient was decreased in the radial direction and increased in the axial and circumferential directions. The variations of hydraulic permeability coefficient from nondegenerate discs (Grade I) to mildly degenerate discs (Grade II) in each direction were significant (P < 0.05). However, the changes in permeability from Grade II to Grade III groups were not significant (P > 0.05) except in the circumferential direction (3.8% increase; P < 0.05). CONCLUSIONS: The hydraulic permeability of human nondegenerate anulus fibrosus is direction-dependent (i.e., anisotropic), with the greatest permeability in the radial direction. With disc degeneration, the radial permeability of anulus fibrosus decreases, mainly because of decreased water content, and the axial and circumferential permeability coefficients increase, mainly because of structural change, leading to more isotropic permeability behavior for Grade III discs.

Age Factors↗
PubMed1999

Association between an aggrecan gene polymorphism and lumbar disc degeneration.

STUDY DESIGN: A case-control study using magnetic resonance imaging findings and a polymerase chain reaction assay to investigate the association between aggrecan gene polymorphism and lumbar disc degeneration. OBJECTIVE: To analyze whether the aggrecan gene polymorphism is related to lumbar disc disease in young women. SUMMARY OF BACKGROUND DATA: It has been suggested that a genetic factor or familial predisposition contributes to the development of lumbar disc herniation. However, the precise genetic component related to disc disease remains unclear. Recently, a polymorphism has been identified in the region of the human aggrecan gene. The expressed variable numbers of tandem repeat polymorphism occur in the highly conserved repeat region. METHODS: The participants were 64 young women with or without low back problems. Magnetic resonance imaging was used to evaluate the degeneration and herniation of the intervertebral disc. Genomic deoxyribonucleic acid was extracted from all participants. A polymerase chain reaction assay was carried out to detect the alleles of the aggrecan gene. The association of intervertebral disc degeneration and herniation with the distribution of the aggrecan gene alleles was analyzed. RESULTS: Findings showed an overrepresentation of alleles with small numbers of repeats in subjects with multilevel disc degeneration, thus indicating a significant distribution difference. There also was a significant difference between the distribution of alleles and the severity of disc degeneration. No significant association was found between any of the alleles either in number or type of disc herniation. CONCLUSIONS: The current study showed that multilevel and severe disc degeneration was present in the participants with shorter variable numbers of tandem repeat length of the aggrecan gene. This suggests that subjects with shorter variable numbers of tandem repeat length of the aggrecan gene have a risk of having multilevel disc degeneration develop at an early age.

Adult↗
PubMed2000

A cross-sectional study correlating lumbar spine degeneration with disability and pain.

STUDY DESIGN: Cross-sectional design. OBJECTIVES: To investigate the correlation between degeneration in the lumbar spine and self-reported disability and pain levels in patients with and without a history of trauma. SUMMARY OF BACKGROUND DATA: The link between lumbar spine degeneration and low back pain remains controversial, as does the correlation between trauma and spinal degeneration. METHODS: Radiographic and questionnaire data were collected from 172 consecutive patients with low back pain. Back pain severity was measured using two scales: one for pain over the entire episode and one for pain during the previous week. All patients also completed the Revised Oswestry Disability Questionnaire before radiography was performed. Further questions concerning the chronicity of symptoms and trauma were included. RESULTS: Controlling for age, patients with low back pain with a history of trauma had a statistically significant increase in the severity of facet degeneration (P < 0.02) compared with nontrauma patients with low back pain. However, there was no difference in disability and pain scores between the trauma and nontrauma patients or between the genders. A weak correlation between pain severity ratings and the number of levels of degeneration and the severity of the degeneration at the disc and facets was noted. CONCLUSIONS: Patients with low back pain with a history of trauma had more severe facet arthrosis than do nontrauma patients with low back pain, but there were no differences in pain and disability. There was a weak correlation between the quantity and severity of lumbar degeneration with pain levels, but not with disability scores. These findings are discussed in the light of recent reports regarding the cervical spine.

Adolescent↗
PubMed2000

Low back pain in relation to lumbar disc degeneration.

STUDY DESIGN: Cross-sectional magnetic resonance imaging (MRI) study. OBJECTIVES: To study the relation of low back pain (LBP) to disc degeneration in the lumbar spine. BACKGROUND DATA: Controversy still prevails about the relationship between disc degeneration and LBP. Classification of disc degeneration and symptoms varies, hampering comparison of study results. METHODS: Subjects comprised 164 men aged 40-45 years-53 machine drivers, 51 construction carpenters, and 60 office workers. The data of different types of LBP, individual characteristics, and lifestyle factors were obtained from a questionnaire and a structured interview. Degeneration of discs L2/L3-L5/S1 (dark nucleus pulposus and posterior and anterior bulge) was assessed with MRI. RESULTS: An increased risk of LBP (including all types) was found in relation to all signs of disc degeneration. An increased risk of sciatic pain was found in relation to posterior bulges, but local LBP was not related to disc degeneration. The risks of LBP and sciatic pain were strongly affected by occupation. CONCLUSIONS: Low back pain is associated with signs of disc degeneration and sciatic pain with posterior disc bulges. Low back pain is strongly associated with occupation.

Adult↗
PubMed2001

Disc height and signal intensity of the nucleus pulposus on magnetic resonance imaging as indicators of lumbar disc degeneration.

STUDY DESIGN: A cross-sectional magnetic resonance imaging (MRI) study of degeneration of the lumbar spine. OBJECTIVES: To compare the usefulness of disc height and that of T2-weighted signal intensity as indicators of disc degeneration. SUMMARY OF BACKGROUND DATA: Disc height and signal intensity have been used as indicators for disc degeneration. Their relation to each other and to early degeneration has not been well documented. There is evidence that physical load can affect disc height. METHODS: Forty-one machine operators, 41 construction carpenters, and 46 office workers, aged 40-45 years, and 22 students aged 18-20 years were examined with sagittal magnetic resonance imaging. All study participants were men. The mean value of the anterior and posterior disc height and the relative T2-weighted signal intensity of the nucleus pulposus of discs L2-L3 to L5-S1 were measured. RESULTS: Young men showed the lowest disc height but the highest relative signal intensity. Disc height showed an increasing trend from the office workers (sedentary) to blue-collar workers (more physical work) at all disc levels but L5-S1. Relative signal intensity showed a decreasing trend for these same worker types at all levels. In generalized linear modeling, signal intensity and the occupations, in reference to the young students, showed a significant effect on disc height. CONCLUSIONS: Relative signal intensity was lower in the middle-aged men than in the young men, indicating age-related disc degeneration. Despite the general positive association between disc narrowing and decreased relative signal intensity, disc narrowing may behave unexpectedly in relation to signal intensity and age. Signal intensity may be a more sensitive measure of disc degeneration. The validity of disc height as an indicator of early degeneration seems questionable.

Adolescent↗
PubMed2002

The sand rat model for disc degeneration: radiologic characterization of age-related changes: cross-sectional and prospective analyses.

STUDY DESIGN: This report is composed of two studies, one cross-sectional and one prospective cohort study, that analyze the radiologic features of disc degeneration in the sand rat (Psammomys obesus). OBJECTIVES: To statistically assess progressive disc degeneration in this useful animal model in terms of a cross-sectional study and a prospective monthly evaluation of individual animals. SUMMARY OF BACKGROUND DATA: P. obesus is an attractive small rodent model for spontaneous age-related disc degeneration. Because disc degeneration is spontaneous, the model avoids use of chemonucleolysis or surgical injury to cause disc degeneration. Little is understood, however, about specific details of the progressive disc deterioration. METHODS: This study statistically assessed 158 animals in a cross-sectional study and 22 animals in a longitudinal study, which followed individual animals to 12 months of age. Radiologic features involving irregular disc margins, disc wedging, disc narrowing, endplate calcification, subchondral sclerosis, ligament calcification, and osteophyte formation were studied. RESULTS: Significant age-related cross-sectional changes were present for all features (P < or = 0.005). Males showed a statistically greater incidence of wedging at 6 and 12 months, wedging at 2 and 6 months, and endplate calcification at 2 months than did females. By 6 months of age, however, endplate calcification had a higher incidence in females than in males. Prospective analysis showed that wedging, narrowing, endplate calcification, and irregular disc margins were more common at 12 months of age than at 2 months (P = 0.0001). By the age of 12 months, all lumbar sites of both males and females showed endplate calcification and the majority of animals showed narrowing and wedging. CONCLUSIONS: Radiographic signs of degeneration were evident by age 2 months; wedging, narrowing, irregular disc margins, and endplate calcification were the most common degenerative changes in older animals. These data show that the sand rat provides a reliable, useful model of spontaneous disc degeneration.

Aging↗
PubMed2002

New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration.

STUDY DESIGN: A new rabbit model was developed that produces disc degeneration through the application of controlled and quantified axial mechanical load. OBJECTIVES: To characterize the changes associated with disc degeneration, and to evaluate the feasibility of local transfer of agents to the compressed discs to stimulate disc regeneration. SUMMARY OF BACKGROUND DATA: Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated is needed. METHODS: New Zealand white rabbits (n = 33) were used for this study. The discs in five animals remained unloaded and served as controls, whereas in 28 animals the discs were axially compressed using a custom-made external loading device. After 1 (n = 7), 14 (n = 7), and 28 (n = 7) days of dynamic loading, or 28 (n = 7) days of loading followed by 28 days of unloaded recovery time, the animals were killed and the lumbar spine was harvested for tissue preparation. Disc height, disc morphology, cell viability, disc stiffness, and load to failure were measured. Recombinant adenovirus encoding for two different marker genes (Ad-Luciferase and Ad-LacZ) was injected into the discs in loaded specimens and the gene expression was measured. RESULTS: The unloaded intervertebral discs of the rabbits consisted of a layered anulus fibrosus, a cartilaginous endplate, and a nucleus pulposus comparable with those of humans. After 14 and 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were not reversible after 28 days of unloading. The stiffness and the load to failure did not change significantly in the discs after 28 days of loading, as compared with the unloaded control discs. Adenovirus-mediated gene transfer to discs was tolerated by all the animals. LacZ gene expression was found 2 weeks after injection of AdLacZ in loaded disc cells. CONCLUSIONS: The results of this study suggest that disc degeneration can be induced by axial dynamic loading in the rabbit intervertebral disc. The compressed rabbit intervertebral discs were large enough for the application of local transmitters through a percutaneous approach. We anticipate that this animal model could be used as a basic model to study intervertebral disc degeneration and to investigate new local therapeutic strategies for maintaining disc health or initiating tissue repair.

Adenoviridae↗
PubMed2004

Experimental disc degeneration due to endplate injury.

The aim of this study was to create an experimental model of disc degeneration that closely mimicked human disc degeneration. In six domestic pigs, an L4 cranial endplate perforation into the nucleus pulposus was made. Three months postoperatively, compressive testing was performed on the L2-L4 motion segments, and intradiscal pressure was measured in the intervening discs. Histochemical and morphologic examinations were made on the excised degenerated and adjacent discs. A significant reduction in water content was observed in the outer anterior annulus of the degenerated disc. In the nucleus, the proteoglycan content was significantly reduced, as well as the cellularity, although not significantly. The nucleus lost its gel-like structure and was discolored, and there was delamination of annular layers. Intradiscal pressure in the nucleus was significantly lower in the degenerated disc. In conclusion, experimental degeneration of the intervertebral disc induced by endplate penetration resembled human disc degeneration, as exemplified by biochemical and structural changes.

Animals↗
PubMed2003

A fibronectin fragment stimulates intervertebral disc degeneration in vivo.

STUDY DESIGN: A radiographic, histologic, biochemical, and gene expression study was conducted in vivo in a rabbit model to determine the effect of injection of the N-terminal 30 kDa fibronectin fragment (Fn-f) into the intervertebral disc along with various control substances. OBJECTIVE: To determine if the Fn-f is able to induce disc degeneration in vivo. SUMMARY OF BACKGROUND DATA: Animal models of disc degeneration are crucial to defining the molecular events involved in disc degeneration. Although spontaneous and induced models of disc degeneration have been described, none is ideal for molecular studies. A better understanding of disc degeneration at the molecular level is necessary to promote rational design of therapies for degenerative disc disease. MATERIALS AND METHODS: Thirty-one New Zealand white rabbits underwent injection of Fn-f and control substances into the central region of separate lumbar discs using a fine needle. Euthanasia was performed at the 2-, 4-, 8-, 12-, and 16-week time points and the discs were examined radiographically, histologically, biochemically, and with gene expression. RESULTS: Radiographs demonstrated anterior osteophyte formation at Fn-f-injected disc spaces by the 12-week time point. Histology demonstrated a progressive loss of the normal architecture of the nucleus pulposus and anulus fibrosus over the 16-week study period. A progressive loss of proteoglycans was documented using GAG assay but total collagen did not appear to change appreciably. Gene expression studies demonstrated a significant down-regulation of both aggrecan and type II collagen mRNA between the 8- and 16-week time points. CONCLUSION: Fn-f appears to induce a progressive degenerative process within the intervertebral disc after injection that resembles degenerative disc disease. This model has several significant advantages for the study of disc degeneration at the molecular level. Further studies are warranted to elucidate the mechanism and molecular events associated with Fn-f-mediated disc degeneration.

Aggrecans↗
PubMed2004

In vivo growth factor treatment of degenerated intervertebral discs.

STUDY DESIGN: An in vivo model was used to investigate the response of degenerated discs to various exogenous growth factors. OBJECTIVES: To study growth factor-induced alterations of the spatial and temporal patterns of disc cellularity and matrix gene expression. SUMMARY OF BACKGROUND DATA: Cell proliferation and proteoglycan synthesis have been stimulated by growth factors in normal disc cells, suggesting that growth factors may play a therapeutic role for degeneration. However, the response in situ in degenerated discs has not been characterized. METHODS: Degeneration was induced in murine caudal discs by static compression. Degenerated discs were given single or multiple injections of growth and differentiation factor-5, transforming growth factor-beta, insulin-like growth factor-1, basic fibroblast growth factor, or saline as control. Comparisons of disc morphology, anular cell density, proliferating cells, disc height, and aggrecan and type II collagen gene expression were made either 1 week or 4 weeks after treatment. RESULTS: In some growth and differentiation factor-5 and transforming growth factor-beta treated discs, expansion of inner anular fibrochondrocyte populations into the nucleus was observed. The cells actively expressed aggrecan and type II collagen mRNA. A lesser effect was observed for insulin-like growth factor-1 and little or no effect for basic fibroblast growth factor. Differences in cell density and proliferating cells were not significant between treatments but suggested a trend of increased cellularity and proliferation following growth factor treatment. A statistically significant increase in disc height 4 weeks after growth and differentiation factor-5 treatment was measured. CONCLUSIONS: Anular fibrochondrocytes in degenerated discs are responsive to some growth factors in vivo. The results have implications in the early intervention of disc degeneration to arrest or slow the degenerative process.

Aggrecans↗
PubMed2006

Possible pathogenesis of painful intervertebral disc degeneration.

STUDY DESIGN: We collected the specimens of lumbar intervertebral disc (i.e., the symptomatic degenerative disc) from patients with discogenic low back pain to study the histopathologic features and growth factor expressions. OBJECTIVES: To study the pathogenesis of disc degeneration, meanwhile discriminating between common disc degeneration (aging disc) (i.e., black asymptomatic disc, not clinically relevant) and painful disc degeneration (i.e., symptomatic disc, clinically relevant). SUMMARY OF BACKGROUND DATA: The pathogenesis of intervertebral disc degeneration is poorly understood, mainly because of the difficulty to establish the experimental model with good reproducibility. Recently, the popularity of spinal fusion leads to more opportunities to obtain disc specimens, which could be applied to explore the pathogenesis of disc degeneration with modern biologic techniques. METHODS: There were 21 specimens of lumbar intervertebral discs from 15 patients with discogenic low back pain during posterior lumbar interbody fusion, 16 aging discs from patients without low back pain, and 10 normal discs as control collected for the study of their histopathologic features, as well as the expressions of basic fibroblast growth factor (bFGF) and its receptor (Flg), transforming growth factor-beta1 (TGF-beta1) and its receptor (TGF-betaRI) by immunohistochemistry. The distribution of macrophages and mast cells was also noted. Proliferating cell nuclear antigen was assessed to evaluate proliferating activities of disc cells. RESULTS: The distinct histologic characteristic of the disc from the patient with discogenic low back pain was the ingrowth of vascularized granulation tissue along torn fissures, extending from the external layer of the anulus fibrosus into the nucleus pulposus. The immunohistochemical staining showed that there were strong expressions of bFGF and TGF-beta1 and their receptors, as well as a strong expression of proliferating cell nuclear antigen in the zones of granulation tissue in the painful discs. However, there were only weak expressions in the nongranulation tissue zones in the painful discs and aging discs, and no expression in the control discs. In addition, abundant macrophages and mast cells were found in the granulation tissue zones of painful discs but absent in the nongranulation tissue zones of painful discs or aging discs and the normal control discs. CONCLUSIONS: The findings indicated that degeneration of the painful disc might originate from the injury and subsequent repair of anulus fibrosus. Growth factors, such as bFGF and TGF-beta1, macrophages and mast cells might play a key role in the repair of the injured anulus fibrosus and subsequent disc degeneration.

Adult↗
PubMed2006

Nerve fiber ingrowth into scar tissue formed following nucleus pulposus extrusion in the rabbit anular-puncture disc degeneration model: effects of depth of puncture.

STUDY DESIGN: In vivo histologic study of nerve ingrowth in the rabbit anular-puncture disc degeneration model. OBJECTIVE: To examine innervation of intervertebral discs and surrounding tissues in the rabbit anular-puncture model with various magnitudes of injury. SUMMARY OF BACKGROUND DATA: A rabbit anular-puncture model of disc degeneration was recently established. However, to our knowledge, the neuropathologic changes in the degenerated disc and surrounding tissues in this model have not been examined. METHODS: Anular punctures with an 18-gauge needle at depths of 1 and 5 mm were randomly performed at the L2-L3 or L4-L5 discs in New Zealand white rabbits (n = 16; 3.0-3.5 kg). The degree of disc degeneration was followed radiographically, and was further evaluated by magnetic resonance imaging and histology at sacrifice 4 or 12 weeks after the puncture. To identify nerve ingrowth into the discs, the L2-L3 to L4-L5 discs were immunostained with an antibody against protein gene product 9.5, a general marker for nerve fibers. RESULTS: Significant decreases in disc height and signal intensity in magnetic resonance imaging were observed only in the 5 mm punctured discs (P < 0.05). In all the discs, including nonpunctured control discs, protein gene product 9.5-immunoreactive fibers were only occasionally observed in the outermost part of the anulus fibrosus. In the 5 mm punctured discs, nucleus pulposus tissues were extruded, and scar tissues formed outside the discs. No nerve ingrowth into the needle track lesion at the anular puncture site was observed. However, protein gene product 9.5-immunoreactive fibers were observed in scar tissues on the surface of the puncture site. This finding was more evident in the 5 mm than in the 1 mm punctured discs (P < 0.05). CONCLUSIONS: This study indicates that in the rabbit anular-puncture disc degeneration model, disc degeneration associated with a higher nerve growth into the scar tissue was more evident when induced by a 5 mm than a 1 mm puncture. Although nerve ingrowth was observed in the extruded disc tissue, nerve ingrowth into the outer anulus, which has been reported in patients with discogenic pain, was not observed during the short observation period in this disc degeneration model. The limitation in assessing pain by behavior analysis or histologic evaluation of nerve ingrowth should be considered. Further studies to identify a surrogate marker of pain should be encouraged.

Animals↗