Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples. Laboratory investigation

OBJECT: In this paper the authors' goal was to identify histological and immunohistochemical differences between cervical disc hemrniation and spondylosis. METHODS: A total of 500 cervical intervertebral discs were excised from 364 patients: 198 patients with disc herniation and 166 patients with spondylosis. We examined en bloc samples of endplate-ligament-disc complexes. Types of herniation and graded degrees of disc degeneration on MR images were examined histologically and immunohistochemically. RESULTS: The herniated discs showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue mainly in the ruptured outer layer of the anulus fibrosus. The vascular invasion was most significant in uncontained (extruded)-type herniated discs. Chondrocytes positive for matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both herniated and spondylotic discs. Free nerve fibers, positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were strongly apparent in and around the outer layer of uncontained (extruded)-type herniated discs, with enhanced expression of NGF. The authors observed that herniated discs showed more advanced degeneration in the outer layer of the anulus fibrosus around the granulation tissue than spondylotic discs. On the other hand, spondylotic discs showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus than herniated discs. Spondylotic discs also had thicker bony endplates and expressed TNFalpha and MMP-3 more diffusely than herniated discs, especially in the inner layer of the anulus fibrosus. CONCLUSIONS: The authors' results indicate that herniated and spondylotic intervertebral discs undergo different degenerative processes. It is likely that TNFa, MMP-3, bFGF, and VEGF expression is upregulated via the herniated mass in the herniated intervertebral discs, but by nutritional impairment in the spondylotic discs. Macrophage accumulation around newly formed blood vessels in the herniated disc tissues seemed to be regulated by MMP-3 and TNFalpha expression, and both herniated and spondylotic discs exhibited marked neoangiogenesis associated with increased bFGF and VEGF expression. Nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus as well as in endothelial cells of the small blood vessels.     

Histological development of intervertebral disc herniation

Sagittal and horizontal sections of 257 intervertebral discs obtained at autopsy and material obtained from 441 operations for herniation of a disc were examined histologically. In the material that was taken at autopsy, myxomatous degeneration of the annulus fibrosus increased in proportion to the age of the subject. The bundles in the internal layer of the annulus fibrosus reversed their usual direction and showed myxomatous degeneration, sometimes resulting in posterior and anterior convex bulging in the internal layer of the anterior and posterior parts of the annulus fibrosus, respectively. When material from a disc was surgically removed as a single free fragment (as in a complete extrusion or a sequestration type of herniation), annulus fibrosus with myxomatous degeneration was found in most material, while the nucleus pulposus rarely was. These results suggest that, from the standpoint of pathomechanism, a protrusion type of herniation of the annulus fibrosus exists in which only the annulus fibrosus is protruded due to reversal of the bundles of the annulus fibrosus, without involvement of the nucleus pulposus. This type of herniation would be a separate entity from the protrusion type of herniation of the nucleus pulposus that occurs when the nucleus pulposus is protruded through a fissure in the annulus fibrosus.     

False-negative lumbar discograms. Correlation of discographic and histological findings in postmortem and surgical specimens

To investigate the causes of false-negative discograms, 181 lower thoracic and lumbar intervertebral discs that had been removed as part of en bloc specimens during thirty autopsies were studied first by discography and then histologically. Comparison of the results of the two methods showed that if fissures and cysts were present in a degenerated anulus fibrosus, but did not establish continuity between the nuclear cavity and the site of a herniation, the discogram was false-negative. Under these circumstances, the inner fiber bundles of the anulus fibrosus were intact and their orientation was often reversed, so that they bulged inward. This finding suggested that a protrusion or a prolapse of tissue from just the anulus fibrosus might have been developing. Ten of the fifty-seven discs that had such changes in the orientation of the fibers had a histologically proved protrusion or prolapse of the anulus fibrosus. However, the discograms showed protrusion in only six of the ten discs and demonstrated a false-negative result in the other four. The cases of seventy-seven patients in whom discography had been performed and a herniation had been subsequently confirmed at operation were also studied. Fifty-nine of the patients had a protrusion and eighteen had a prolapse of the disc. The discograms were falsely interpreted as negative in 32 per cent (nineteen) of the fifty-nine patients who had a protrusion and in 56 per cent (ten) of the eighteen who had a prolapse. Histologically, the prolapses were interpreted as protrusions of a portion of the anulus fibrosus. It was concluded that false-negative discograms are more frequent when a protrusion or a prolapse involves the anulus fibrosus rather than the nucleus pulposus, and that a negative discogram does not exclude the possibility of extensive degeneration of the anulus fibrosus.     

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.     

Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc degeneration, which supports the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. This study was supported by a grant from the AO/ASIF Foundation Switzerland (00-B72) and a grant from the AO Spine (SRN 02/103).     

Age-related changes in fibromodulin and lumican in human intervertebral discs.

STUDY DESIGN: An analysis of proteoglycans of the intervertebral disc using immunoblotting of tissue extracts. OBJECTIVES: To investigate the changes in structure and abundance of fibromodulin and lumican in human intervertebral discs during aging and degeneration. SUMMARY OF BACKGROUND DATA: Fibromodulin and lumican are keratan sulfate proteoglycan constituents of the disc's extracellular matrix, whose interaction with collagen fibrils may contribute to the mechanical properties of the tissue. Changes in their abundance and/or structure that occur with aging and degeneration therefore may have an impact on disc function. METHODS: Lumbar intervertebral discs were obtained from individuals of different ages, and extracts of anulus fibrosus and nucleus pulposus were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using antibodies specific for fibromodulin and lumican. RESULTS: The major changes in abundance observed with age were a decrease in fibromodulin in the adult nucleus pulposus and an increase in lumican in anulus fibrosus during early juvenile development. In addition, fibromodulin in the anulus fibrosus exhibited a structural change with increasing age, characterized by a shift toward the predominance of its glycoprotein form lacking keratan sulfate. Fibromodulin was more abundant in the anulus fibrosus than in nucleus pulposus at all ages, whereas lumican was much more abundant in nucleus pulposus than in anulus fibrosus in the young juvenile; in the adult, however, lumican was present in comparable levels in both tissues. With increasing degrees of degeneration, fibromodulin exhibited an increase in abundance. CONCLUSIONS: Growth, aging, and degeneration of the intervertebral disc are associated with changes in the abundance and structure of fibromodulin and lumican, which presumably influence the functional properties of the tissue.     

纤维环穿刺诱导椎间盘退变动物模型的实验研究

目的：探讨纤维环穿刺诱导椎间盘退变建立动物模型的可行性。方法：新西兰大白兔24只，用持针器夹持18G皮肤穿刺针从左前外侧刺人L3/4、L4/5、L5/6椎间盘的纤维环，深度控制在5mm。术前及术后3、6、10周对造模后的椎间盘及对照的椎间盘（L2／3）行MRI检查，并行免疫组化及组织学观察。结果：术后第3周到第10周，造模后的椎间盘MRI T2WI信号呈现持续减弱趋势，免疫组化及组织学观察发现髓核细胞的数量及Ⅱ型胶原含量较对照间盘进行性减少（P〈0．01）。结论：纤维环穿刺法可以诱导兔椎间盘的缓慢退变，为研究椎间盘的退行性变提供有效的动物模型。     

Localization of cathepsins D, K, and L in degenerated human intervertebral discs.

STUDY DESIGN: Localization of cathepsins D, K, and L in degenerated intervertebral discs was examined by immunohistochemistry. OBJECTIVES: To determine the involvement of cathepsins in the pathomechanism of intervertebral disc degeneration by monitoring the immunolocalization of cathepsins in degenerated intervertebral disc tissue. SUMMARY OF BACKGROUND DATA: Cathepsins D, K, and L are enzymes that contribute to the matrix destruction seen in the articular cartilage affected by osteoarthritis and rheumatoid arthritis. However, little is known about the contribution of these cathepsins to intervertebral disc degeneration. METHODS: Paraffin-embedded sections of degenerated intervertebral disc tissue collected at the time of surgery (13 discs from 12 patients) were immunohistochemically stained with antibodies for cathepsins D, K, and L. For further characterization of the stained cells, immunohistochemical detection of CD68 and TRAP staining were performed. RESULTS: Hematoxylin and eosin staining revealed obvious signs of degeneration in all sections. Cathepsins D and L were immunolocalized in disc fibrochondrocytes at various sites exhibiting degeneration. Cathepsins K were found in tartrate-resistant acid phosphatase-positive multinucleated cells, in particular near the cleft within the cartilaginous endplate. However, few cells were positive for these cathepsins in anulus fibrosus that maintained the lamellar structure of collagen fibers. CONCLUSIONS: Marked expression of cathepsins D and L was observed at the site of degeneration. Cathepsins D and K localized in tartrate-resistant acid phosphatase-positive multinucleated cells existed at the cleft between the cartilaginous endplate and vertebral body. The site-specific localization of these cathepsins suggests the association of these proteinases with endplate separation and disorganization of the anulus fibrosus in degenerative spinal disorders.     

Lumbar intervertebral herniation. The composition of free sequesters--a morphologic study]

Since 1934 when surgery for lumbar disc herniation was first performed various forms of disc herniation have been described. It is generally accepted that disc herniations can be classified as follows: disc protrusion, disc prolapse, and free sequestration. Histological evaluations of protruded and prolapsed disc have been presented in literature, revealing degenerative changes. No special attention was given to free sequestered disc elements. The aim of this paper was to analyse the frequency of freely sequestered intervertebral disc fragments and to investigate the morphologic nature of sequestered discs. The free sequesters were observed in 15.5% of all operated cases (N = 187). In 16 (55.2%) of these cases the sequester was composed of nucleus pulposus material, in 12 (41.4%) cases end-plate elements were noted and in one case (3.4%) anulus fibrosus elements were found.     

Neural elements in human cervical intervertebral discs.

This study attempted to characterize neural elements within the human cervical intervertebral disc. Cervical intervertebral discs were obtained from four adult human subjects at autopsy. Discs were stained in bulk with gold chloride, sectioned, and viewed with the light microscope. Nerve fibers appeared to enter the disc in the posterolateral direction and course both parallel and perpendicular to the bundles of the anulus fibrosus. Nerves were seen throughout the anulus but were most numerous in the middle third of the disc. Receptors resembling Pacinian corpuscles and Golgi tendon organs were seen in the posterolateral region of the upper third of the disc. These results provide further evidence that human cervical intervertebral discs are supplied with both nerve fibers and mechanoreceptors.     

Observations on fiber-forming collagens in the anulus fibrosus

STUDY DESIGN: The spatial distribution of fiber-forming collagens in the anulus fibrosus was investigated in the complete longitudinal and horizontal sections of human lumbar intervertebral discs of seven individuals. OBJECTIVES: To obtain a more detailed structural definition of the anulus fibrosus because structural alterations of its collagen fiber network have been implicated in discal degeneration and other spinal pathologies. SUMMARY OF BACKGROUND DATA: Prior biochemical or immunofluorescence studies permitted only limited conclusions concerning the spatial distribution of the fiber-forming collagens in relation to anatomic structures because they were based on intraoperative tissue specimens or performed on incomplete sections of human intervertebral discs. METHODS: Complete human intervertebral discs with their adjacent vertebral bodies were fixed, decalcified, and embedded in paraffin. The intervertebral disc and its adjacent structures were reviewed in their entirety on one histologic slide. Monoclonal antibodies against human Types I, II, and III collagen were used for immunohistochemistry. A comparative analysis based on both immunohistochemical and histologic evaluation was performed. RESULTS: Type I collagen was seen abundantly in the outer zone and outer lamellas of the inner zone of the anulus fibrosus. On longitudinal sections, the Type I collagen distribution took the shape of a wedge. On horizontal sections, the Type I collagen positive area took the shape of a ring that was wider anteriorly than posteriorly. This suggests that the three-dimensional shape of the Type I collagen-positive tissue in the anulus fibrosus can be described by a donut that is wider anteriorly than posteriorly. Type II collagen was present in the entire inner of the anulus fibrosus, but not in the outer zone. In addition, it was found in the cartilaginous endplates. Type III collagen showed some codistribution with Type II collagen, particularly in pericellular locations in areas of spondylosis, which was noted at the endplates, vertebral rim, and insertion sites of the anulus fibrosus. CONCLUSIONS: These observations on the location of Types I and II collagen provide a more detailed structural definition of the anulus fibrosus, which may assist in further investigation of discal herniation.     

Histology of intervertebral disc protrusion: an experimental study using an aged rat model

STUDY DESIGN: In vitro experimental intervertebral disc ruptures of aged rats were examined histologically. OBJECTIVES: To clarify the mechanism of intervertebral disc herniations by microscopic investigation of ruptured discs. SUMMARY OF BACKGROUND DATA: Clinically, disc herniations have been classified into two types: extrusion and protrusion. However, the pathogenesis of protrusion type herniations has not yet been demonstrated by any studies. To clarify this issue, it is essential to establish an appropriate model producing disc herniations, and to examine the sequential changes in the structure of herniated discs. METHODS: Lumbar discs of 2-year-old rats were examined histologically and compared with human lumbar discs. To examine structural changes in discs subjected to repetitive motion stress, 400 repetitions of a sequence of flexion (30 degrees ) and axial rotation (6 degrees ) were applied in vitro to the lumbar discs of the animals. RESULTS: The microstructure of normal lumbar discs in aged rats was similar in many ways to the human lumbar discs in a 20- to 40-year-old adult. Of 10 discs subjected to repetitive stress, 4 were ruptured at the junction between the posterior anulus fibrosus and the sacral cartilage endplate. One had an extruded nucleus pulposus, and three had a protruded anulus fibrosus, which displayed disorganized structure containing widened and flaccid lamellae. CONCLUSIONS: The results from this study indicate that disc protrusion can be caused by disorganization of the ruptured annular lamellae, not by focal compression of the nucleus pulposus.     

A clinicopathological study of cervical intervertebral discs--Part 1: On histopathological findings

In order to examine the aging process of the cervical intervertebral discs, a histopathological study was performed on 158 cervical discs obtained at autopsy from 37 individuals ranging in age from 3 months to 87 years. In the nucleus pulposus, degenerative changes consisting of myxomatous and slightly hyalinized degeneration were already seen in the specimens obtained from subjects in the third decade of life. Degenerative changes of the annulus fibrosus, however, tended to develop from the fourth decade of life, with myxomatous degeneration mainly in the anterior and hyalinized degeneration in the posterior annulus. The horizontal fissure of the annulus extending to its outer portion was seen more frequently in the posterior portion. In the cartilaginous plate of the vertebral body, fissure formation and degeneration became evident in the fifth decade of life. In contrast to the disc, repairing processes were observed in the cartilaginous plate. Spur formation at the corner of the vertebral body may be due to the degeneration of the outer layer of the disc leading to enchondral ossification.     

Age changes to the anulus fibrosus in human intervertebral discs.

This study deals with age changes in the anulus fibrosus of the lumbar intervertebral discs of human individuals 21-83 years of age. The anular laminas from individuals less than 40 years of age consisted of obliquely orientated collagen fibers exhibiting a pennate arrangement. These fibers were intensely argyrophilic after silver nitrate impregnation. The fibers and surrounding substance appeared light pink after exposure to the periodic-acid-Schiff (PAS) reaction and blue with alcian blue complex. Beginning during middle age and continuing into the eighth decade, there was a progressive degeneration of the laminas. The breakdown of the intact laminas was characterized by the fraying, splitting, and loss of collagen fibers. The newly formed spaces became filled with intense PAS-positive material. In addition, there was a continual deposition of chondroid substance in the anuluses of the aging discs. This phenomenon was not seen in the young disc. These age related changes lead to a loss of integrity to the disc, which may be a factor in disc pathology.     

Gene expression of collagen types IX and X in the lumbar disc

To study gene expression of collagen typesIX and X in human lumbar intervertebral discs duringaing and degeneration and to explore the role of collagentypes IX and X in disc degeneration.     

Myxomatous degeneration of the lumbar intervertebral disc

Sixteen patients were operated on for lumbar pain and pain radiating into the sciatic nerve distribution. In all 16, when the anulus fibrosus was incised, soft, gray disc material extruded under pressure like toothpaste being squeezed from a tube. This syndrome of myxomatous degeneration is a distinct entity, different from classical fibrotic disc degeneration or herniated nucleus pulposus. Surgical removal associated with partial facetectomy produced excellent results. The concept of incompetence of the anulus fibrosis is discussed.     

A pathologic study of lumbar disc herniation in the elderly

Twenty-nine fragments from herniated lumbar discs of patients over 60 years of age were studied pathohistologically. For comparison, 109 discs from patients under 59 years of age also were observed. They were classified into seven types according to their composition. In 70% of discs from patients between 60 and 69 and in 80% of discs from patients over 70, the fragments were composed of the anulus fibrosus and the cartilaginous end-plate. The authors concluded that the cartilaginous end-plate had avulsed from the vertebral body and herniated with the anulus fibrosus in these cases. This type of herniation occurs more often than herniation of the nucleus pulposus over 30, and may be most common in elderly patients because of their advanced disc degeneration.     

The innervation of the cervical intervertebral discs

Microdissection and histologic studies were undertaken to determine the innervation of the cervical intervertebral discs. The cervical sinuvertebral nerves were found to have an upward course in the vertebral canal, supplying the disc at their level of entry and the disc above. Branches of the vertebral nerve supplied the lateral aspects of the cervical discs. Histologic studies of discs obtained at operation showed the presence of nerve fibers as deeply as the outer third of the anulus fibrosus. These anatomic findings provide the hitherto missing substrate for primary disc pain and the pain of provocation discography.     

Histochemical and ultrastructural observations on brown degeneration of human intervertebral disc

Thirty-eight fresh human intervertebral discs collected during anterior interbody fusion surgery were histochemically and ultrastructurally analyzed for pigments. Macroscopically, five stages of degeneration were classified according to the color, fibrosis, and fragility of the nucleus pulposus of the discs. In order to demonstrate lipofuscin granules, specimens were subjected to special staining procedures, including carbol fuchsin lipofuscin stain, the Schmorl's reaction, and autofluorescence. Lipofuscin granules were distributed from the inner layer of the annulus fibrosus to the nucleus pulposus. Such granules were numerous in cases of slight or severe degeneration, whereas fewer granules were found in cases of moderate degeneration. However, the stage of macroscopic degeneration of the intervertebral disc did not necessarily correlate with the incidence of lipofuscin granules. By ultrastructural observation, the morphological features of the components of the intervertebral disc and the ultrastructure of the lipofuscin granule were clarified. The ultrastructure of the "brown degeneration" disc exhibited markedly increased amorphous electron-dense bodies located among collagen fibrils in the matrix.     

Cell deformation and micromechanical environment in the intervertebral disc

The purpose of this research was to explore the in situ anatomic and mechanical environment of disc cells. Laser scanning confocal microscopy was used to characterize three-dimensional morphology of intervertebral disc cells, micromechanical deformation and interaction with extracellular matrix, and functional intercellular communication. Bovine coccygeal discs were used for both the anatomic and micromechanical investigations. Anulus fibrosus cells had a complex morphology with sinuous processes woven into the extracellular matrix, particularly in the outer aspect of the anulus where they were also interconnected via functional gap junctions. They were also found in an extensive pericellular matrix of type-VI collagen, joining as many as ten cells into linear cell arrays that could be extracted from the matrix as functional units. Mechanically, collagen fibril sliding was demonstrated to govern cell mechanics and strain transfer in the anulus fibrosus during loading activities. Lamellar cells were largely protected from direct tensile strains in the matrix, with minimal intercellular strains. However, intercellular strains between lamellar cells in adjacent arrays were large, illustrating shearing between linear cell arrays. Appreciable shear was observed across the lamellar cell bodies as well as to the cellular processes woven into the matrix. These findings demonstrated the morphologic and micromechanical complexity of anulus fibrosus cells. The knowledge of the in situ environment of disc cells will provide a base to investigate the mechanical implications of disc degeneration on the cellular environment and to better understand how mechanical and genetic risk factors can impact the cells that are essential to maintaining the intervertebral disc.