Spontaneous Age-related Cervical Disc Degeneration in the Sand Rat

Background

Disc space narrowing, osteophytes, and disc degeneration are common and increase with aging. Few animal models are appropriate for the study of spontaneous age-related cervical disc degeneration.

Questions/purposes

We used the sand rat, a member of the gerbil family with well-recognized age-related lumbar disc degeneration, to determine whether spontaneous cervical disc degeneration differed from lumbar degeneration when evaluated by (1) radiologic and (2) histologic measures. Animals 2 to 25 months of age were used in these analyses.

Methods

Cervical and lumbar discs of 99 sand rats were analyzed with radiology, and cervical discs of 67 sand rats were studied with histology. Lateral digital radiographs of cervical and lumbar spines were scored for presence or absence of wedging, disc space narrowing, osteophytes, end plate calcification, and irregular disc margins at C2-C3 through C6-C7 and T12-L1 through L7-S1. Percentages for presence were calculated and statistically analyzed for younger (range, 2-11.9 months old) versus older (range, 12.0-25 months old) animals.

Results

Cervical discs in younger animals exhibited a greater proportion of irregular margins compared with lumbar sites (94% versus 83%; p = 0.02; 95% CI for difference, 2.7, 19.0%). In older animals, cervical discs showed a greater proportion of osteophytes than did lumbar discs (7% versus 0%; p < 0.0001). The incidence of disc space narrowing was greater in cervical versus lumbar sites (99% versus 90%; p = 0.0008). Cervical spine sites which contained osteophytes morphologically showed irregular disc margins and revealed an extrusion of herniated disc material in the osteophytes.

Conclusions

Radiologic and morphologic studies confirmed age-related disc degeneration in the cervical spine of the sand rat.

Clinical Relevance

Clinical cervical aging studies have shown that 14% of asymptomatic subjects younger than 40 years have abnormal MRI scans with an increase to 50% by 50 years old. We studied an economic rodent model for cervical age-related spontaneous disc.     

In vivo biofunctional evaluation of hydrogels for disc regeneration

Purpose

Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model.

Methods

In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted.

Results

Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration.

Conclusions

None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.     

Protective effect of CDDO-ethyl amide against high-glucose-induced oxidative injury via the Nrf2/HO-1 pathway

Background Context

Intervertebral disc degeneration (IDD) is the main cause of low back pain, and nucleus pulposus (NP) cell apoptosis is an important risk factor of IDD. However, the molecular mechanism of this disease remains unknown.

Tandem age-related lumbar and cervical intervertebral disc changes in asymptomatic subjects

Purpose

To investigate the frequency of tandem lumbar and cervical intervertebral disc degeneration in asymptomatic subjects.

Methods

We evaluated magnetic resonance imaging (MRI) results from 94 volunteers (48 men and 46 women; mean age 48 years) for age-related intervertebral disc degeneration in the lumbar and cervical spine.

Results

MRI indicated degenerative changes in the lumbar spine in 79 subjects (84 %), with decreased disc signal intensity in 74.5 %, posterior disc protrusion in 78.7 %, anterior compression of the dura in 81.9 %, disc space narrowing in 21.3 %, and spinal canal stenosis in 12.8 %. These findings were more common in older subjects at caudal levels. MRI showed degenerative changes in both the lumbar and cervical spine in 78.7 % of the volunteers.

Conclusions

Degenerative findings in both the lumbar and cervical spine, suggesting tandem disc degeneration, was common in asymptomatic subjects. These results provide normative data for evaluating patients with degenerative lumbar and cervical disc diseases.     

Effect of applying p75NTR saporin to a punctured intervertebral disc on calcitonin gene-related peptide expression in rat dorsal root ganglion neurons

Background

Recent studies have revealed that the low-affinity nerve growth factor receptor, p75 neurotrophin receptor (p75NTR), is important in inflammatory pain. Moreover, p75NTR immunoreactive sensory nerve and dorsal root ganglion (DRG) neurons have been found to innervate lumbar intervertebral discs. The purpose of the current study was to investigate the effect of p75NTR saporin, a toxin used to destroy p75NTR, on calcitonin gene-related peptide (CGRP), an inflammatory neuropeptide associated with pain, in DRG neurons innervating punctured intervertebral discs in rats.

Methods

The neurotracer fluorogold (FG) was applied to the surfaces of L5/6 discs to label their innervating DRG neurons (n = 30). Of 30 rats, 10 were in a nonpunctured disc sham surgery control group (nonpuncture group), and the other 20 were in experimental groups in which intervertebral discs were punctured with a 23-gauge needle. p75NTR saporin was applied to the discs of 10 rats (puncture + p75NTR saporin group) and the other 10 received the same volume of saline (puncture + saline group). At 14 days after surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for CGRP, and the proportions of CGRP-immunoreactive DRG neurons was evaluated.

Results

Of the FG-labeled neurons innervating the L5/6 disc, the proportion of CGRP-immunoreactive neurons was 32% ± 6% (mean ± SE) in the nonpuncture group, 47.2% ± 8% in the puncture + saline group, and 34.6% ± 9% in the puncture + p75NTR saporin group. The proportion of CGRP-immunoreactive neurons was significantly greater in the puncture + saline group compared with the nonpuncture and puncture + p75NTR saporin groups (P < 0.01).

Conclusions

Half of the DRG neurons innervating the discs were positive for CGRP in the puncture + saline group. CGRP is important for mediating inflammatory and nerve-injured pain and may be important in discogenic pain. However, p75NTR saporin suppressed CGRP expression in DRG neurons. Therefore, p75NTR may be an important receptor for mediating discogenic pain via CGRP expression.     

Assessment of apparent diffusion coefficient in lumbar intervertebral disc degeneration

Objective

The aim of this study was to determine the relationship between the apparent diffusion coefficient (ADC) and lumbar intervertebral disc degeneration using diffusion-weighted magnetic resonance imaging (DWI).

Materials and methods

Using a 3 T magnetic resonance scanner, DWI of the lumbar spine was assessed in 109 patients, with a total of 545 lumbar discs analyzed. Apparent diffusion coefficient values were recorded for each disc, and all discs were visually graded by two independent observers using Pfirrmann’s grading system. Apparent diffusion coefficient values of disc were tested by correlation with qualitative clinical grading of degeneration severity, patient age, and sex. Correlations were investigated using Pearson’s and Spearman’s rank correlation analysis, and multiple regression analysis.

Results

Intervertebral disc degeneration was negatively correlated with ADC values of all levels (Spearman’s correlation coefficient ranged from ?0.381 to ?0.604, p < 0.001). There was a significant negative association between age and ADC values at all spinal levels (Pearson’s correlation coefficient ranged from ?0.353 to ?0.650, p < 0.001). When stepwise regression models were analyzed, both disc degeneration and age remained negatively associated with ADC values at each lumbar level (standardized coefficients ranged from ?0.231 to ?0.505, p < 0.01 and standardized coefficients ranged from ?0.179 to ?0.523, p < 0.05 respectively).

Conclusion

Apparent diffusion coefficient values obtained using DWI can assess lumbar intervertebral disc degeneration, and the ADC values were negatively correlated with the degree of disc degeneration.     

Is an annular tear a predictor for accelerated disc degeneration?

Purpose

It is questionable whether an annular tear (AT) is a predictor for accelerated degeneration of the intervertebral discs. The aim of the present study was to answer this question via a matched case–control study design that reliably eliminates potential confounders.

Materials

Presence or absence of AT, defined as a hyperintense lesion within the annular fibrosus on T2-weighted non-contrast MRI images, was documented in 450 intervertebral lumbar discs of 90 patients who could be followed up for at least 4 years with MRI. Discs with an AT (n = 36) were matched 1:1 to control discs according to the level, degree of initial disc degeneration on MRI (both Pfirrmann grade median 4, range 3–4), age (59.5 ± 15.0 versus 59.3 ± 14.6 years), BMI (26.7 ± 4.4 versus 26.9 ± 4.4 kg/m²) and interval to the follow-up MRI (4.8 ± 0.9 versus 5.1 ± 0.8 years). The degree of disc degeneration after a minimum of 4 years was graded on the follow-up MRI in both groups according to the Pfirrmann classification.

Results

One-fourth (25 %) of the 36 discs with an AT on the initial MRI exam progressed in degeneration. This was similar to the rate of the matched control discs with no AT, in which also around one-fourth (22 %) showed a progression of degeneration (p = 1.00), also without any difference in the degree of degeneration.

Conclusion

Discs with a Pfirrmann grade >2 with an AT, defined by a hyperintense signal intensity on MRI, are not prone to accelerated degeneration if compared to discs without an AT. Therefore, the presence of an AT per se does not predict accelerated disc degeneration.     

Quantitative MRI analysis of the surface area, signal intensity and MRI index of the central bright area for the evaluation of early adjacent disc degeneration after lumbar fusion

Purpose

The aim of this study was to evaluate early ASD at short-term follow-up in fused and unoperated patients with degenerative disc disease, using quantitative magnetic resonance imaging (MRI) analysis of the area, signal intensity and their product, i.e., MRI index of the central bright area of the disc as well as measures of intervertebral disc height and Pfirrmann grading scale. The further purpose was to determine whether fusion accelerates ASD compared with non-surgical treatment in short-term follow-up.

Methods

One hundred and eight chronic low back patients diagnosed as L4/L5 degeneration undertook either one-level instrumented posterior lumbar interbody fusion or conservative treatment. They were followed up for about 1?year. Finally 46 fused and 45 conservatively treated patients with MRI follow-up were included. Pre- and post-treatment MRIs were compared to determine the progression of disc degeneration at the two cranial adjacent segments.

Results

The area, signal intensity and MRI index of the central bright area of the adjacent discs decreased in the operated and unoperated groups from pre-treatment to follow-up, except for an insignificant decrease of signal intensity at the second adjacent segment in the unoperated group. The changes in these parameters were statistically greater at the first than the second adjacent segment in the fused group, but not in the unoperated group. And the changes in the fused group were more pronounced than those at both neighbouring levels in the unoperated group. However, the Pfirrmann grading scale and intervertebral disc height did not detect any changes at adjacent discs in either group.

Conclusions

Decrease in the parameters of quantitative MRI analysis indicated early degeneration at discs adjacent to lumbar spinal fusion. Fusion had an independent effect on the natural history of ASD during short-term follow-up. Continued longitudinal follow-up is required to determine whether these MRI changes lead to pathologic changes.     

Interference in the endplate nutritional pathway causes intervertebral disc degeneration in an immature porcine model

Purpose

Previous studies have shown that blocking the endplate nutritional pathway with bone cement did not result in obvious intervertebral disc degeneration (IDD) in mature animal models. However, there are very few comparable studies in immature animal models. As vertebroplasty currently is beginning to be applied in young, even biologically immature patients, it is important to investigate the effect of cement blocking at the endplate in an immature animal model.

Methods

Two lumbar intervertebral discs in eight immature pigs were either blocked by cement in both endplate pathways or stabbed with a scalpel in the annulus fibrosus (AF) as a positive control, and with a third disc remaining intact as a normal control. Magnetic resonance imaging (MRI) and histology study were performed.

Results

After three months, the cement-blocked discs exhibited severe IDD, with the percentage of disc-height index (DHI), nucleus pulposus (NP) area, and NP T2 value significantly lower than the normal control. These IDD changes were histologically confirmed. Post-contrast MRI showed diseased nutritional diffusion patterns in the cement-blocked discs. Moreover, the degenerative changes of the cement-blocked discs exceeded those of the injured AF positive controls.

Conclusions

The endplate nutritional pathway was interfered with and diseased after three months of bone cement intervention in an immature porcine model. Severe interference in the endplate nutritional pathway in an immature porcine model caused IDD. These findings also draw attention to the fact that interference in endplate nutritional pathways in immature or young patients may affect the vitality of adjacent discs.     

Kinematic study of the relation between the instantaneous center of rotation and degenerative changes in the cervical intervertebral disc

Purpose

We located the instantaneous center of rotation (ICR) for the cervical spine at various ages and investigated age-related changes. We evaluated the impact of cervical disc degeneration on the ICR using a scoring system based on plain radiographs.

Methods

Flexion, extension, and neutral lateral radiographs were obtained from 680 asymptomatic subjects (363 men, 317 women; ages 20–79 years) divided into six 10-year-age groups. The ICRs from C3/C4 to C6/C7 were determined from the radiographs using MIMICS software. A scoring system determined from lateral radiographs quantitatively assessed degeneration of cervical intervertebral discs. ICRs were compared among groups to analyze age-related changes and the relation between degenerative changes and ICR location.

Results

In asymptomatic subjects, the ICR was located approximately at the superior half of the lower vertebral body height and the posterior half of its width. The ICR at the C5/C6 level was located more anterior and higher in patients >50 years than in younger subgroups (P < 0.05). Degenerative changes produced more anterosuperior translation of the ICR, which was significantly correlated with height loss (P < 0.05). In moderately or severely degenerated segments, the ICR location change reached statistical significance (P < 0.05).

Conclusions

Baseline data for Chinese cervical spine ICRs were established for the third through eighth decade of life, including age-related changes and the kinematic effects of degenerative change on the ICR in the functional spine unit. These findings should be considered in clinical practice and when designing disc prostheses.     

NSAID use in intervertebral disc degeneration: what are the effects on matrix homeostasis in vivo?

Background Context

Non-steroidal anti-inflammatory drugs (NSAIDs) are a widely used treatment for low back pain (LBP). Literature on NSAID use in articular cartilage has shown detrimental effects; however, minimal data exist to detail the effects of NSAIDs in intervertebral disc degeneration (IDD). As IDD is a major cause of LBP, we explored the effects of indomethacin, a commonly used NSAID, on disc matrix homeostasis in an animal model of IDD.

Accelerated premature stress-induced senescence of young annulus fibrosus cells of rats by high glucose-induced oxidative stress

Purposes

Diabetes mellitus (DM) is thought to be an important aetiological factor in intervertebral disc degeneration. A glucose-mediated increase of oxidative stress is a major causative factor in development of diseases associated with DM. The aim of this study was to investigate the effect of high glucose on mitochondrial damage, oxidative stress and senescence of young annulus fibrosus (AF) cells.

Methods

AF cells were isolated from four-week-old young rats, cultured, and placed in either 10 % FBS (normal control) or 10 % FBS plus two different high glucose concentrations (0.1 M and 0.2 M) (experimental conditions) for one and three days. We identified and quantified the mitochondrial damage and reactive oxygen species (ROS) (oxidative stress). We also identified and quantified the occurrence of senescence and telomerase activity. Finally, the expressions of proteins were determined related to replicative senescence (p53-p21-pRB) and stress-induced senescence (p16-pRB).

Results

Two high glucoses enhanced the mitochondrial damage in young rat AF cells, which resulted in an excessive generation of ROS in a dose- and time-dependent manner for one and three days compared to normal control. Two high glucose concentrations increased the occurrence of senescence of young AF cells in a dose- and time-dependent manner. Telomerase activity declined in a dose- and time-dependent manner. Both high glucose treatments increased the expressions of p16 and pRB proteins in young rat AF cells for one and three days. However, compared to normal control, the expressions of p53 and p21 proteins were decreased in young rat AF cells treated with both high glucoses for one and three days.

Conclusions

The present study demonstrated that high glucose-induced oxidative stress accelerates premature stress-induced senescence in young rat AF cells in a dose- and time-dependent manner rather than replicative senescence. These results suggest that prevention of excessive generation of oxidative stress by strict blood glucose control could be important to prevent or to delay premature intervertebral disc degeneration in young patients with DM.     

Migration Inhibitory Factor Enhances Inflammation via CD74 in Cartilage End Plates with Modic Type 1 Changes on MRI

Background

Type 1 Modic changes are characterized by edema, vascularization, and inflammation, which lead to intervertebral disc degeneration. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine closely related to the inflammatory cytokines detected in degenerative intervertebral disc tissues. However, the existence and role of MIF and its receptor CD74 in intervertebral disc degeneration have not been elucidated.

Questions/purposes

We asked whether (1) MIF and its receptor CD74 are expressed in cartilage end plates with Type 1 Modic changes, (2) MIF is associated with cartilage end plate degeneration, (3) the MIF antagonist (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) suppresses MIF-induced inflammatory cytokine release, and (4) inflammatory cytokines are released by cartilage end plate chondrocytes via CD74 by activating the CD74 antibody (CD74Ab).

Methods

We examined MIF and CD74 expression by human cartilage end plate chondrocytes and tissues with Type 1 Modic changes from eight patients using immunocytofluorescence and immunohistochemistry. MIF production by the chondrocytes was assessed by ELISA and PCR. We compared cytokine release by chondrocytes treated with MIF in the presence or absence of exogenous ISO-1 by ELISA. Cytokine release by chondrocytes after treatment with CD74Ab was determined by ELISA.

Results

MIF was expressed in degenerated human cartilage end plate tissues and chondrocytes. Lipopolysaccharide and tumor necrosis factor α (TNF-α) upregulated MIF expression and increased MIF secretion in chondrocytes in a dose-dependent manner. MIF increased the secretion of IL-6, IL-8, and prostaglandin E2 (PGE2) in a dose-dependent manner. ISO-1 reduced the secretion of IL-6, IL-8, and PGE2. CD74Ab activated CD74 and induced release of inflammatory cytokines.

Conclusions

Chondrocytes in cartilage end plate with Type 1 Modic changes express MIF and its receptor CD74. MIF might promote the inflammatory response through CD74. MIF-induced cytokine release appears to be suppressed by ISO-1, and CD74Ab could induce cytokine release.

Clinical Relevance

The MIF/CD74 pathway may represent a crucial target for treating disc degeneration since inhibiting the function of MIF with its antagonist ISO-1 can reduce MIF-induced inflammation and exert potent therapeutic effects.     

Intervertebral disc cell- and hydrogel-supported and spontaneous intervertebral disc repair in nucleotomized sheep

Purpose

Regenerative repair is a promising new approach in treating damaged intervertebral discs. An experimental scheme was established for autologous and/or allogenic repair after massive disc injury.

Methods

Disc healing was promoted in 11 animals by injecting in vitro expanded autologous/homologous disc cells 2?weeks after stab injury of lumbar discs L1-2. The following control discs were used in our sheep injury model: L2-3, vehicle only; L3-4, injury only; L4-5, undamaged; and lumbar discs from four non-experimental animals. Disc cells were suspended in a biologically supportive albumin/hyaluronan two-component hydrogel solution that polymerizes when inserted in order to anchor cells at the injection site. The parameters studied were MRI, DNA, glycosaminoglycan, collagen content, histology, immunohistology for collagens type I, II and aggrecan, and mRNA expression of GAPDH, β-actin, collagen type I, II, X, aggrecan, lubricin, and IL-1β.

Results

All parameters demonstrated almost complete healing of the injured discs after 6?months, when compared with data from both the endogenous non-injured controls as well as from the healthy animals.

Conclusion

Sheep experience spontaneous recovery from disc injury. The process of endogenous repair can be enhanced by means of hydrogel-supported cells.     

Dose- and time-dependent effect of high glucose concentration on viability of notochordal cells and expression of matrix degrading and fibrotic enzymes

Purpose

Diabetes mellitus is an important aetiological factor in intervertebral disc degeneration. The disappearance of notochordal cells in the nucleus pulposus is thought to be the starting point for intervertebral disc degeneration. A cellular effect of diabetes mellitus on apoptosis of notochordal cells and intervertebral disc degeneration has been recently reported. However, how the duration and severity of diabetes mellitus affects viability of notochordal cells and intervertebral disc degeneration is still unknown .

Methods

Rat notochordal cells were isolated, cultured, and placed in either 10 % foetal bovine serum (FBS) (normal control) or 10 % FBS plus three different high glucose concentrations (0.1 M, 0.2 M, and 0.4 M) (experimental conditions) for one, three, five and seven days, respectively. We identified and quantified the degree of proliferation and apoptosis, caspase activities, and cleavages of Bid and cytochrome-c. In addition, we examined the cells for expression of matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs).

Results

Each three high glucose concentrations significantly decreased proliferation and increased apoptosis of notochordal cells from culture days one to seven in a dose-dependent manner. Compared with those of 10 % FBS, caspase-9 and -3 activities and cleavage of Bid and cytochrome-c were significantly increased in each three high glucose concentrations, accompanied by increased expression of MMP-1, -2, -3, -7, -9, and -13 and TIMP-1 and -2.

Conclusions

High glucose concentration significantly decreased proliferation and increased apoptosis of notochordal cells via the intrinsic pathway with dose- and time-dependent effects. We also found that expression of MMPs and TIMPs was increased with dose- and time-dependent effects. Therefore, these results suggest that aggressive glucose control from an early stage of diabetes mellitus should be recommended to prevent or limit intervertebral disc degeneration.     

Radiological study on disc degeneration of thoracolumbar burst fractures treated by percutaneous pedicle screw fixation

Objective

To examine disc degeneration at levels adjacent and next adjacent to the fractured vertebra and to analyses, if the disc degeneration is determined by the endplate fracture.

Summary of background data

Thoracolumbar burst fracture is one of the most common spinal injuries. The diagnostic (clinical and imaging) approach and treatment of a fractured vertebra is well established; however, some controversy remains. The associated disc degeneration is less well known after 9–12 months of the short segment pedicle screw fixations. There is a major controversy whether spinal trauma with vertebral endplate fractures can result in posttraumatic disc degeneration. No study to date, however, has assessed disc degeneration of the AO type A3 thoracolumbar fractures without neurologic deficits after pedicle screw fixations.

Methods

Twenty-six patients with single-level AO type A3 thoracolumbar fractures and no neurological deficit were treated by using postural reduction and short segment percutaneous pedicle screw fixation. No laminectomy and fusion were performed. Implants were removed 9–12 months after the first operation. The thoracolumbar magnetic resonance imaging (MRI) was used to assess disc degeneration at levels adjacent and next adjacent to the fractured vertebra before the first operation and after the second operation in a retrospective study.

Results

After the instrumentation removal, new disc degeneration was usually found at level adjacent to the cranial endplate of fractured vertebra by MRI examination in 24 patients. The average Pfirrmann grade of degenerative discs adjacent to the cranial fractured endplates deteriorated from 2.1 pre-operatively to 3.4 after the second operation. No change of disc degeneration was seen at the caudal disc space adjacent to the fractured vertebra and the levels next adjacent to the fractured vertebra. The discs next adjacent to the fractured vertebra were showed to be relatively normal without changes of degeneration during the study period.

Conclusions

Disc degeneration usually occurs at level adjacent to the fractured endplate of thoracolumbar burst fractures. Endplate fracture is strongly associated with disc degeneration. No correlation between fixation level and disc degeneration is seen in this study.     

Vertebral Bodies or Discs: Which Contributes More to Human-like Lumbar Lordosis?

Background

The attainment of upright posture, with its requisite lumbar lordosis, was a major turning point in human evolution. Nonhuman primates have small lordosis angles, whereas the human spine exhibits distinct lumbar lordosis (30°–80°). We assume the lumbar spine of the pronograde ancestors of modern humans was like those of extant nonhuman primates, but which spinal components changed in the transition from small lordosis angles to large ones is not fully understood.

Questions/Purposes

We wished to determine the relative contribution of vertebral bodies and intervertebral discs to lordosis angles in extant primates and humans.

Methods

We measured the lordosis, intervertebral disc, and vertebral body angles of 100 modern humans (orthograde primates) and 56 macaques (pronograde primates) on lateral radiographs of the lumbar spine (humans–standing, macaques–side-lying).

Results

The humans exhibited larger lordosis angles (51°) and vertebral body wedging (5°) than did the macaques (15° and ?25°, respectively). The differences in wedging of the intervertebral discs, however, were much less pronounced (46° versus 40°).

Conclusions

These observations suggest the transition from pronograde to orthograde posture (ie, the lordosis angle) resulted mainly from an increase in vertebral body wedging and only in small part from the increase in wedging of the intervertebral discs.     

Lovastatin prevents discography-associated degeneration and maintains the functional morphology of intervertebral discs

Background context

Discography is an important diagnostic approach to identify the painful discs. However, the benefit of discography, a procedure involving needle puncture and injection of the diagnostic agent into the intervertebral disc, is controversial and has been reported to be associated with accelerated degeneration.

Purpose

To investigate the effect of lovastatin on the prevention of degeneration caused by a discography simulation procedure in rat caudal discs.

Study design

In vivo study using rat caudal discs.

Methods

A single flexible 27-gauge needle puncture into rat caudal discs was performed under fluoroscopic monitoring. Different concentrations (0.1, 1, 5, and 10 μM) of lovastatin were prepared and injected into randomly chosen caudal discs. RNA expression of selected genes, histologic, and immunohistochemical staining were performed to evaluate the phenotypic effects of lovastatin on rat caudal discs.

Results

Simulation of the discography procedure by puncturing the rat caudal discs with a 27-gauge needle and injection of saline solution induced degenerative changes in the nucleus pulposus with minimal damage to the annulus fibrosus. Aggrecan, Type II collagen, and SOX9 expressions were upregulated, whereas Type I collagen expression was significantly suppressed in discs treated with 5 and 10 μM lovastatin. Discs treated with 5 and 10 μM lovastatin were subjected to alcian blue staining and immunohistochemistry that revealed higher levels of glycosaminoglycans and an increase in the number of cells producing S-100 proteins, Type II collagen, and bone morphogenetic protein-2 (BMP-2), respectively. The most effective phenotypic repair was observed in discs treated with 10 μM lovastatin.

Conclusions

Intradiscal administration of lovastatin solution upregulated the expressions of BMP-2 and SOX9 and promoted chondrogenesis of rat caudal discs after needle puncture and substance injection. Therefore, we suggest that lovastatin promotes disc repair and can be used as a potential therapeutic agent for biological repair of disc degeneration after the diagnostic discography procedure.