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Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits.

STUDY DESIGN: A study of the disc height and biochemical changes in the rabbit intervertebral disc after injection of osteogenic protein-1 into the nucleus pulposus. OBJECTIVES: To evaluate the in vivo effects of osteogenic protein-1 administered intradiscally to the intervertebral disc of rabbits. SUMMARY OF BACKGROUND DATA: Growth factors, such as osteogenic protein-1 and transforming growth factor-beta, have the ability to stimulate synthesis of proteoglycan and collagen in vitro. No attempts have yet been made to determine the effects of these growth factors in an in vivo model. METHODS: Twenty-four New Zealand adolescent white rabbits were divided evenly into two subject groups. In one group, three consecutive intervertebral discs were injected with saline; whereas in the other group, they were injected with osteogenic protein-1 in saline. At 2, 4, and 8 weeks after the injection, the intervertebral disc heights of the injected specimens were measured by lateral plain radiographs and compared with preinjection measurements. The change in disc height was expressed as the percent disc height index compared with the preinjection value. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, proteoglycan, and collagen contents. RESULTS: At 2 weeks after the injections, the mean disc height index of the osteogenic protein-1-injected discs was 15% greater than that of the saline group. The increase in disc height with osteogenic protein-1 injection was still statistically significant at the 4- and 8-week time points. The proteoglycan content of the nucleus pulposus in discs injected with osteogenic protein-1 was higher than that in the saline group at the 2-week time point. The osteogenic protein-1-induced effect on the proteoglycan content was also present at the 4- and 8- week time intervals; however, these increases were not statistically significant. There were no significant differences in the DNA content, normalized to noninjected control, of the nucleus pulposus between the saline and osteogenic protein-1 groups. However, a significant increase in the DNA content of the anulus fibrosus in the osteogenic protein-1 group, compared with that of the anulus fibrosus in the saline group, was observed after 4 weeks. CONCLUSION: To date, no study has demonstrated the potential in vivo effects of growth factors on the intervertebral disc. The present study reports that the intradiscal administration of osteogenic protein-1 in vivo results in an increased disc height present at 2, 4, and 8 weeks and an increase in PG content of the nucleus pulposus at the 2-week time point. Therefore, osteogenic protein-1 may act to stimulate metabolic activity in the nucleus pulposus. Continued research is needed to evaluate the potential of growth factor-induced reversal of age-related disc degeneration in an appropriate animal model. In addition, studies in a nonhuman primate animal model will be essential before considering intradiscal injection of growth factors in humans.

Age Factors↗

[Influence of colchicine upon morphology of intervertebral disc of rabbit].

The morphological changes of intervertebral disc of rabbit in the culture liquids of containing colchicine was observed by microscopy and transmission microscopy and hydroxyproline density of culture liquids was measured by stages. Meanwhile, set up control groups. Undiscovery that colchicine can produce discolysis and shrinking. We regard as major mechanism of colchicine treating herniated of intervertebral disc is anti-inflammation and anti-microtubule. We advance opposite viewpoint for Michael R. Rask's hypothesis which colchicine can produce herniated of intervertebral disc shrinking.

Animals↗

Cell mechanics and mechanobiology in the intervertebral disc.

STUDY DESIGN: A review is presented on current knowledge of the micromechanical factors in the intervertebral disc, their role in modifying cell biology, and changes with degeneration. OBJECTIVES: To identify current knowledge, knowledge gaps, and areas for future research in micromechanics of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Mechanical factors play important roles in the initiation and progression of intervertebral disc degeneration. Evidence suggests that substantial biologic remodeling occurs in the intervertebral disc in response to mechanical stimuli that may play a critical role in determining the fate of a degenerating intervertebral disc. Information is needed on the precise mechanical stimuli that these cells experience and the mechanisms that govern their responses. METHODS: A review is presented of cell morphology, cell mechanics, and the internal strains and other mechanical factors predicted to occur at the cell level. A review of intervertebral disc cell responses to well-controlled physical stimuli is also presented with a focus on in vitro studies of explants and isolated cells. RESULTS: Important differences in cell morphology, mechanics, micromechanical factors, and mechanobiology are noted to occur between cells of the nucleus pulposus and anulus fibrosus. Changes in these features with degeneration are critically understudied, particularly degeneration-associated changes in cell morphology, cell mechanics, and altered physiology with mechanical loading. CONCLUSIONS: Information on the mechanisms that govern cell responses to mechanical stimuli in the intervertebral disc are just emerging. Studies must address determination of the factors that control micromechanical stimuli, but also mechanisms by which mechanics may interact with genetic factors to regulate expression and remodeling of extracellular matrix molecules, cytokines and mediators of pain and inflammation in degenerating tissue.

Biomechanical Phenomena↗

Nerve ingrowth into diseased intervertebral disc in chronic back pain.

BACKGROUND: In the healthy back only the outer third of the annulus fibrosus of the intervertebral disc is innervated. Nerve ingrowth deeper into diseased intervertebral disc has been reported, but how common this feature is and whether it is associated with chronic pain are unknown. We examined nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain. METHODS: We collected 46 samples of intervertebral discs from 38 patients during spinal fusion for chronic back pain. 30 samples were from pain levels clinically established by discography and 16 samples were from adjacent vertebral levels with no pain. We obtained 34 control samples of intervertebral disc from previously healthy individuals with normal histology within 8 h of recorded death. We used standard immunohistochemical techniques to test for a general nerve marker, a nociceptive neurotransmitter (substance P), and a protein expressed during axonogenesis (growth-associated protein 43 [GAP43]). FINDINGS: We identified nerve fibres in the outer third of the annulus fibrosus in 48 (60%) of the 80 samples of intervertebral discs. Nerves were restricted to the outer or middle third of the annulus fibrosus in the 34 control samples. Among the patients with chronic low back pain, nerves extended into the inner third of the annulus fibrosus and into the nucleus pulposus in 21 (46%) and ten (22%) samples, respectively. Nerves usually accompanied blood vessels, but in 14 of the samples from back-pain patients, isolated nerve fibres were seen in the discal matrix. Both types of nerve fibres expressed substance P, but only non-vessel-associated fibres expressed GAP43. Deep nerve ingrowth into the inner third of the annulus fibrosus, the nucleus pulposus, or both was seen in four (25%) of 16 biopsy samples from non-pain levels and in 17 (57%) samples from pain levels. Of the 16 paired samples from both pain and non-pain levels, five pain-level samples and one non-pain-level sample showed deep nerve ingrowth. INTERPRETATION: Our finding of isolated nerve fibres that express substance P deep within diseased intervertebral discs and their association with pain suggests an important role for nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain.

Adult↗

[BMP and LMP-1 for intervertebral disc regeneration].

Some evidence indicates that intervertebral disc degeneration is associated with decreasing of matrix synthesis from disc cell. BMP-2 increased mRNA of aggrecan and Type II collagen. It also enhanced disc matrix (proteoglycan) production. Adenovirually mediated LMP-1 overexpression in intervertebral disc cells increased disc cell proteoglycan production through BMP-2 and BMP-7 mediated process.

Adaptor Proteins, Signal Transducing↗

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↗

The radiological symptoms of lumbar disc herniation and degenerative changes of the lumbar intervertebral discs.

BACKGROUND: The x-ray examination is one of the fundamental diagnostic modalities in patients with low-back-pain. The aim of study was to establish relation between radiological findings and herniation type and its localization. As well, we looked for relation between radiological findings and progression of disc degeneration. MATERIAL/METHODS: The study enrolled 187 individuals operated due to lumbar disc herniation. In each case the x-ray examination of lumbar spine was performed. Herniation was classified as protrusion, prolapse or disc sequestration. According to localization, herniation was defined as central, lateral or intermediate. Removed discs were histologically evaluated to determine degeneration symptoms. The radiological picture was related to the degeneration of the intervertebral discs. RESULTS: The statistical analysis revealed the only one relation -between traction osteophytes and herniation classified as disc prolapse (p<0.05). We found no relations between other radiological findings (narrow intervertebral space, diminished lordosis, scoliosis) and herniation and its localization within the spinal canal. Also there is no relation between disc degeneration and radiological findings. CONCLUSIONS: Classic x-ray examination presents low value in diagnostics of lumbar disc degeneration and its herniation. There is no relation between radiological picture and intensity of degenerative changes within the lumbar discs.

Adult↗

Growth factors and treatment of intervertebral disc degeneration.

STUDY DESIGN: Literature review. OBJECTIVE: To review the most recent findings of the effects of growth factors on the intervertebral disc and, further, to discuss trends in the biologic repair of the degenerated intervertebral disc. SUMMARY OF BACKGROUND DATA: Since early in 1990, advancements in molecular biology and cell culture technology have enabled researchers to accumulate knowledge about the in vitro actions of growth factors on intervertebral disc cells. More recently, the use of growth factors for the biologic regeneration of the intervertebral disc is of increasing interest to the orthopedic field, and indeed, some preliminary in vivo studies have proven their efficacy. METHODS: Based on a literature search conducted using available databases, such as the National Library of Medicine, as well as data presented at scientific conferences held in the past 2 years, primarily in the United States, the current status of biologic therapy for disc degeneration using growth factors was summarized. RESULTS: With increasing evidence to support the feasibility of biologically regenerating intervertebral disc tissues, the clinical application of growth factors has become more plausible. The effects of growth factors on the metabolism of intervertebral disc cells or tissues have been extensively studied using in vitro approaches. More recently, the efficacy of an injection of growth factor protein to reverse disc regeneration has been shown in vivo using a small animal disc degeneration model. The confirmation of those effects and a detailed dose-response study, as well as a long-term safety study, in a large animal model is highly anticipated. Hopefully, the expansion of the clinical use of improved imaging techniques for the early detection of disc degeneration and promising results about the effects of growth factors on intervertebral disc regeneration will benefit the human population in the near future. CONCLUSIONS: The results from these in vitro and in vivo studies reviewed here clearly suggest the potential usefulness of growth factor injections as a new approach to restore intervertebral disc degeneration at an early stage.

Animals↗

Artificial intervertebral disc replacement using bioactive three-dimensional fabric: design, development, and preliminary animal study.

STUDY DESIGN: A new artificial intervertebral disc was developed, and its intrinsic biomechanical properties, bioactivity, and the effectiveness as a total disc replacement were evaluated in vitro and in vivo. OBJECTIVES: To introduce a new artificial intervertebral disc and to evaluate the in vitro mechanical properties, fusion capacity to bone, and segmental biomechanics in the total intervertebral disc replacement using a sheep lumbar spine. SUMMARY OF BACKGROUND DATA: The loss of biologic fusion at the bone-implant interface and prosthetic failures have been reported in previous artificial discs. There have been no clinically applicable discs with detailed experimental testing of in vivo mechanics and interface fusion capacity. METHODS: The artificial intervertebral disc consists of a triaxial three-dimensional fabric (3-DF) woven with an ultra-high molecular weight polyethylene fiber, and spray-coated bioactive ceramics on the disc surface. The arrangement of weave properties was designed to produce mechanical behavior nearly equivalent to the natural intervertebral disc. Total intervertebral disc replacement at L2-L3 and L4-L5 was performed using 3-DF disc with or without internal fixation in a sheep lumbar spine model. The segmental biomechanics and interface histology were evaluated after surgery at 4 and 6 months. RESULTS: The tensile-compressive and torsional properties of prototype 3-DF were nearly equivalent to those of human lumbar disc. The lumbar segments replaced with 3-DF disc alone showed a significant decrease of flexion-extension range of motion to 28% of control values as well as partial bony fusion at 6 months. However, the use of temporary fixation provided a nearly physiologic mobility of the spinal segment after implant removal as well as excellent bone-disc fusion at 6 months. CONCLUSION: An artificial intervertebral disc using a three-dimensional fabric demonstrated excellent in vitro and in vivo performance in both biomechanics and interface histology. There is a potential for future clinical application.

Animals↗

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.

Adult↗

[Vascular proliferation within the herniated lumbar intervertebral discs in surgically treated patients].

Blood vessels are observed in intervertebral discs of children, and after individuals skeletal maturity the intervertebral discs become avascular structures. According to some opinions, new vessels in the annulus fibrosus can appear in adults as a result of regeneration processes. The lumbar intervertebral discs resected during surgery due to low-back-pain and during autopsies (control group) were evaluated histologically. The vascular proliferation was observed in 35% of surgical specimens in all types of herniation (protrusio, prolapse, and free sequesters). The statistical analysis revealed that proliferation take place mainly in young individuals.

Adult↗

Type-II collagen gene expression is transiently upregulated in experimentally induced degeneration of rabbit intervertebral disc.

To clarify phenotypic alterations of intervertebral disc cells during the repair process, we cloned partial type-II collagen cDNA from rabbits and analyzed the level of expression of type-II collagen mRNA in disc degeneration. An animal model was created by surgical denucleation of rabbit intervertebral discs through an extraperitoneal approach. Eight animals each from an experimental and a control group were killed at 2, 4, 8, or 16 weeks postoperatively, and the disc samples were used for this study. Round chondrocyte-like cells that filled the herniated space showed intense signal of type-II collagen mRNA and significant pericellular immunostaining of type-II collagen but no clear staining of type-I collagen. Northern blot analysis revealed that the expression of type-II collagen mRNA of the repair disc cells was transiently increased at 4 weeks postoperatively. The cells were able to change their morphology in response to mechanical stimulation by surgical denucleation and to induce a significant increase in the gene expression of type-II collagen at an early phase of disc degeneration. The present results indicate the transient enhancement of repair activity in the degenerative process of injured fibrocartilage.

Animals↗

Morphology of the cervical intervertebral disc: implications for McKenzie's model of the disc derangement syndrome.

Studies which have examined the cervical intervertebral disc have demonstrated that it is not morphologically similar to the lumbar intervertebral disc. Yet review of the clinical literature has revealed that clinicians have often based clinical theories on the assumption that the cervical and lumbar discs do have a similar structure. The purpose of this paper is to review the literature regarding the morphology of the cervical intervertebral disc in relation to McKenzie's clinical theories which claim that the nucleus pulposus of the adult cervical intervertebral disc may be repositioned. Discussion of the proposed biological mechanisms underlying examination and treatment techniques is imperative if the basis of these techniques is to be better understood.

Journal Article↗

Postmortem changes in ultrastructures of the mouse intervertebral disc.

To elucidate the effects of nutrition and oxygen deficiencies on the intervertebral disc, cell components of mouse intervertebral discs and their postmortem changes were observed by electron microscopy. The annulus fibrosus could be divided into an inner and outer region. The main cell components of the annulus fibrosus were fibroblast-like cells in the outer region and chondrocytes in the inner region. The nucleus pulposus consisted of massively packed notochordal cells. The cartilage plates could also be divided into two zones: articular cartilage and growth cartilage containing chondrocytes. Postmortem degenerative changes proceeded from the peripheral to the central parts of the intervertebral disc, ie, showing degeneration of first the fibroblast-like cells, next the chondrocytes, and finally, the notochordal cells. The findings suggest that cells situated at the periphery predominantly depend on aerobic metabolism, whereas the cells situated more centrally depend on anaerobic metabolism. Furthermore, postmortem changes of the nucleus pulposus were similar to age-related changes. The age-related changes or degeneration in the intervertebral disc appear to be related to deficiencies of nutrition or oxygen caused by changes in structures of the disc and the surrounding tissues.

Animals↗

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↗

Gene expression changes in an early stage of intervertebral disc degeneration induced by passive cigarette smoking.

STUDY DESIGN: This study attempts to determine the molecular changes in intervertebral disc degeneration of rats induced by passive cigarette smoking. OBJECTIVES: To quantitate and compare the gene expression levels in intervertebral discs from passively cigarette smoking rats and nonsmoking rats. SUMMARY OF BACKGROUND DATA: The molecular mechanism of intervertebral disc degeneration has been investigated mainly in vitro but little in vivo, and gene expression analysis has been performed in a few studies. The cigarette smoking is a risk factor of low back pain. We developed a smoking box to create a rat model of intervertebral disc degeneration induced by passive cigarette smoking. METHODS: Total RNA was extracted from intervertebral discs of rats that were raised in a cigarette-smoking box for 2 to 7 weeks. After synthesis of cDNA, the quantitative analysis of gene expression was performed by the real-time PCR. The remaining spines were subjected to the histologic examination. RESULTS: Histologic changes of the nucleus pulposus and the anulus fibrosus were detected after 2 weeks of smoking and were frequently found after 7 weeks. Collagen genes were downregulated remarkably after 7 weeks of smoking. No significant increase was observed in the expressions of matrix metalloproteinase-3, but the expression of tissue inhibitor of metalloproteinases-1 started to increase at 4 weeks of smoking. Aggrecan also started to be up-regulated at 4 weeks. CONCLUSIONS: Changes in gene expression by passive cigarette smoking precede the histologic changes in the intervertebral discs. Reactions to suppress the destruction of tissue matrix and to regenerate the intervertebral discs are occurring at the same time as the degenerative histologic changes.

Animals↗

Regulation of intracellular pH by bovine intervertebral disc cells.

Extracellular acidity is an important determinant of intervertebral disc matrix turnover, possibly exerting effects through changes of intracellular pH (pHi). There is, however, little information concerning the ways in which these cells regulate their pHi. Fluorimetric techniques have been used in the present study to measure pH in isolated intervertebral disc cells, and to characterise the membrane transport pathways by which it is regulated. Nucleus pulposus cells were obtained from bovine intervertebral discs by standard enzymatic digestion techniques, and loaded with the PH-sensitive fluoroprobe BCECF. Resting pHi was approximately 6.7 for cells suspended in either HEPES buffered (HBS) or CO2/HCO3--buffered (BBS) media. Intrinsic buffering capacity was approximately 19 mM pH unit(-1) in HBS and was increased when cells were suspended in BBS. A combination of ion substitution and inhibitor studies for cells at steady-state pH or acidified by exposure to NH4Cl revealed that in HBS Na+ x H+ exchange and an H+-ATPase extrude acid from these cells. Only one of these two systems, the Na+ x H+ exchanger, exhibited a sensitivity to pH, identifying it as the regulator of pH under these conditions. In BBS, an additional pathway which was dependent on extracellular Na+, extracellular HCO3- and intracellular Cl- was detected. These properties are consistent with the four ion HCO3--dependent transporter, although the cation-rich, anion-poor extracellular matrix of the intervertebral disc means that such a pathway has only a marginal role in disc cell pHi regulation.

Animals↗

Type III collagen in the intervertebral disc.

Several collagen types have now been isolated from the intervertebral disc, although type III collagen has previously only been extracted from human pathological disc. In this study, type III collagen has been isolated from normal human and bovine intervertebral disc and immunolocalized in sections of rat, sheep, bovine and 'normal' human intervertebral disc of various ages. Staining with antisera to type III collagen is localized primarily around the cells. Results indicate that cells of the disc sit in 'chondrons', similar to those seen in the deep and mid zones of articular cartilage. We suggest that type III collagen is present in the intervertebral disc and hypothesize that it may be involved in the organization of the pericellular environment, perhaps linking the chondron capsule to the interterritorial matrix.

Animals↗