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The important function of the endplate is to transmit stress and supply nutrition. Endplate degeneration might induce or promote degeneration of the intervertebral disc, causing a series of spine diseases that seriously impair people’s health and life quality. Endplate chondrocytes can respond to mechanical stimulation, which is an important factor affecting endplate degeneration. Inappropriate mechanical stimulation will accelerate endplate degeneration. This review summarized the effects of mechanical stimulation on vertebral endplate chondrocyte apoptosis, synthesis inhibition, calcification, and extracellular matrix degradation. The endplate degeneration induced by mechanical stimulation is regulated by a complex network of signal pathways composed of various signal transduction factors. The signal pathways involved in this review included NF-κB, Wnt, Hedgehog, MAPK, RhoA/Rock-1, AKT/mTOR, TGF-β signaling pathway and miRNA related signals. The interconnection of these pathways was highlighted and summarized. Multiple signaling pathways work together to regulate endplate chondrocyte metabolism, which ultimately leads to the endplate degeneration. This review might shed light on early diagnosis and precise treatment of cartilage endplate degeneration.
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BACKGROUND: Full-understanding of the mechanism of microRNA (miRNA) in the process of intervertebral disc degeneration at the cellular and molecular levels can provides new idea for the early prevention or treatment of a series of spinal diseases to intervertebral disc degeneration. OBJECTIVE: To summarize the research status of the role of miRNA in the cause and mechanism of intervertebral disc degeneration. METHODS: A computed-based online retrieval of PubMed, Wanfang and CNKI databases was conducted with the keywords of “miRNA, intervertebral disc degeneration, extracellular matrix, apoptosis, autophagy, cartilage endplate, nucleus pulposus, fibrous ring” in English and Chinese, respectively. Finally 58 eligible articles were included for review. RESULTS AND CONCLUSION: The role of miRNA in intervertebral disc degeneration has been widely studied, and some of the specific mechanisms have been verified. Most of the studies are limited to the nucleus pulposus, and there are few reports on cartilage endplate and annulus fibrosus. With the in-depth study of miRNA, there is still much space for clinical research.
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Aim To investigate the effect of TaorenHonghua drug pair on intervertebral disc degeneration (IVDD) in rats.Methods Fifty healthy Wistar rats were randomly divided into control group,model group,sham group,meloxicam group and Taoren-Honghua drug pair group,with 10 rats in each group.We established dynamic and static forces imbalance of cervical disc degeneration model or sham surgery in rats.12 weeks later,rats were intragastrically administered with meloxicam,Taoren-Honghua drug pair or saline for 30 days.C4/5 and C6/7 discs were harvested from rats.ABOG staining was used for observation of intervertebral disc morphology,real time PCR for mRNA expressions of type Ⅱ collagen (Col Ⅱ) and type Ⅹ collagen (Col Ⅹ),and immunohistochemical staining for Col Ⅱ and Col Ⅹ.Results Compared with model group,Col Ⅱ expression increased,while Col X expression decreased in chondrocyte of intervertebral disc in Taoren-Honghua-treated group(P ＜ 0.01).Conclusion Taoren-Honghua drug pair could delay the degeneration of cartilage endplate in rat intervertebral disc.
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Objective To study the relationship between degenerative lumbar spondylolisthesis and degeneration of cartilage endplate by magnetic resonance imaging.Methods The median sagittal scanning of LA/L5 and L5/S1 intervertebral discs of all subjects were performed by magnetic resonance imaging with T2.Measureed the inclination angle of the front half of the endplate and the inclination angle of the posterior half of the endplate,then the ratio of the anterior horn and the posterior horn was calculated as the change rate of the endplate.The differences of the rate of cartilage endplate in the corresponding stage of spondylolisthesis group and normal group were compared.Results In L4 lumbar spondylolisthesis group,both upper and lower endplate of L4/L5 intervertebral disc have significant differences between the lumbar spondylolisthesis group and the normal group (t =11.280,-3.765,P =0.000).In L5 lumbar spondylolisthesis group,there are significant differences between the lumbar spondylolisthesis group and the normal group (t =11.280,-3.765,P =0.000),both upper and lower endplate of L5/S1 intervertebral disc;and significant differences were found among the upper and lower endplates of the L5/S1 (t =4.633,P =0.000).Among all the subjects,between the upper and lower endplate of L4/L5,significant differences were found,too(t =17.377,3.137,2.199,P =0.000,0.005,0.035).In addition to the above,the differences were not statistically significant.Therefore,lumbar spondylolisthesis can lead to degenerative in cartilage endplate of Slippage stage.Conclusion The degree of degeneration of the anterior and the posterior half of the same cartilage endplate is asymmetrical,for example,the degeneration of the posterior half of the upper endplate is worse than that of the anterior half of the plate,but the degeneration of the anterior half of the lower endplate is worse than that of the posterior half endplate.The degenerative degree of cartilage endplate was less affected by lumbar spondylolisthesis in the non slip stage.
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<p><b>OBJECTIVE</b>To study the effect of Bushen Huoxue decoction on calcification of cartilage endplate in lumbar vertebrae.</p><p><b>METHODS</b>Six healthy male gerbils with 2-month-old were selected as normal control group, and 24 7-month-old healthy male gerbils were fed to 12-month-old to establish the aged gerbil model. Thirty gerbils were randomly divided into five groups as follow: the normal control group (=6), model group (=6, normal saline 4 ml/kg, intragastric 30 d), Bushen Huoxue low dose group(=6, 1.9× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue middle dose group(=6, 3.8× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), Bushen Huoxue high dose group(=6, 7.6× 10⁻ ³ ml/g given Bushen Huoxue recipe orally, 30 d), the intervention group administered for 1.36 g from 7-month-old age, 30 d. The animals were sacrificed at the age of 2 months in the normal control group and 12 months of age in the other groups. The morphology of the lumbar vertebral cartilage endplate, the area of vascular bud, the ratio of non-calcified/calcified layer were analysis by HE chromosome visual method. The expression of type X collagen and BMPs in cartilage endplates were detected by rabbit monoclonal immunohistochemical staining.</p><p><b>RESULTS</b>The relative area of the vascular buds cartilage endplate measurements showed that compared with the model group, middle dose group and normal control group increased (<0.05), high and low dose groups all had different degrees of increase, but no statistical significance(>0.05). The ratio of cartilage endplate thickness of non-calcified/calcified showed that compared with the model group, Bushen Huoxue middle dose, normal control group increased, with statistical significance(<0.05), and high and low dose groups all had different degrees of increase, but there were no statistical significance(>0.05). Compared with the model group, the expression of type X collagen in the cartilage endplate of the normal group, the Bushen Huoxue low, middle and high dose groups decreased, and had statistical significance(<0.01); compared with the model group, the expression of BMPs in the normal group, Bushen Huoxue middle dose group increased, with statistically significant(<0.01), while the high and low dose groups increased in different degrees, but there was no statistical significance(>0.05).</p><p><b>CONCLUSIONS</b>Bushen Huoxue prescription can delay the calcification of cartilage endplate in the process of aging, suggesting that it can be used as a preventive medicine for early disc degeneration.</p>
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Objective To observe the osteogenic and/or chondrogenic differentiation potential of cartilage endplate derived stem cells ( CESCs) .Methods The cartilage endplate ( CEP) was obtained from 5 patients who underwent posterior discectomy procedure for the lumber degenerative disease.The agarose culture was used to select CESCs.The expanded CESCs were injected into the hydroxyapatite ceram-ic(HA) and incubated for 7 days.After that,the HA contained CESCs were implanted into the subcutaneous of nude mouse for 7 weeks.Then the HA was obtained and sliced for the specific stain and immunohistochemisty.The expanded CESCs were injected into the degenerated in-tervertebral disk of the rabbit for 16 weeks.Then MRI was used to detect the repair of the degenerated disc.Results The metachromasia of toluidin blue indicated that cartilage matrix was formed in the vacant space of HA.Mallory stain indicated that there was bone matrix was formed.The results of immunohistochemistry indicated that there was more collageⅠand collageⅩ,and a small quantity of collage Ⅱ.MRI results indicated that the CESCs could be induced into the chondrocyte-like cells in the rabbit intervertebral disk.Conclusion The CESCs could be induced into the bone/cartilage in vivo.
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Objective To explore the effect of caspase-9 inhibitor on low fetal bovine serum ( FBS)-induced apop-tosis in cartilage endplate chondrocytes in SD rat vertebrae.Methods Disc cartilage endplates were obtained from 3-month old SD rats and subjected to sequential digestion to harvest chondrocytes for primary culture, and apoptosis was in-duced by 1%FBS for 48 hours.Three groups of chondrocytes were treated by 1% FBS, caspase-9 inhibitor ( Z-LEHD-FMK) and DMSO, respectively.After 48 hours, apoptosis was detected by DAPI staining and flow cytometry.The expres-sion of procaspase-9, active caspase-9 and active caspase-3 was monitored by Western blot.Results Compared with the 1%FBS group (40.8 ±0.84)%and DMSO group (40.2 ±1.56)%, the apoptosis rate of the caspase-9 inhibitor group (26.3 ±2.56)% was significantly lower (P<0.05).The expressions of active caspase-9 and active caspase-3 in the caspase-9 inhibitor group were significantly lower than those in the other two groups (P<0.05).Conclusions Caspase-9 inhibitor can inhibit low FBS-induced apoptosis in cartilage endplate chondrocytes of rat vertebrae, and might become a new drug for the treatment of disc degeneration.
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OBJECTIVES@#To investigate the effect of osteoporosis and intervertebral disc degeneration on the endplate cartilage injury in rats.@*METHODS@#A total of 48 female Sprague Dawley rats (3 months) were randomly divided into Groups A, B, C and D with 12 rats in each group. Osteoporosis and intervertebral disc degeneration composite model, simple degeneration model and simple osteoporosis model were prepared in Groups A, B and C respectively. After modeling, four rats of each group at 12th, 18th and 24th week were sacrificed. Intervertebral height of cervical vertebra C6/C7 was measured. Micro-CT was used to image the endplate of cephalic and caudal cartilage at C6/C7 intervertebral disc. Abraded area rate of C6 caudal and C7 cephalic cartilage endplate was calculated, and then C6/C7 intervertebral disc was routinely embedded and sectioned, stained with safranin O to observe histological changes microscopically.@*RESULTS@#At 12, 18 and 24 weeks, intervertebral disc height of C6/C7 were (0.58±0.09) mm, (0.53±0.04) mm and (0.04±0.06) mm in Group A rats, (0.55±0.05) mm, (0.52±0.07) mm and (0.07±0.05) mm in Group B rats. At 24th week, intervertebral disc height of Group A rats was significantly lower than that of Group B rats (P0.05). At 12 and 18 weeks, the abraded rate of C6 caudal and C7 cephalic cartilage endplate in Group A rats were significantly higher than that in Groups B, C and D rats (P0.05). Microscopic observation of CT showed that ventral defects in C6 caudal or C7 cephalic cartilage endplate in Groups A and B appeared after 12 weeks of modeling; obvious cracks were found in front of the C6 and C7 vertebral body, and cartilage defect shown the trend of "repairing" at 18 and 24 weeks after modeling.@*CONCLUSIONS@#Intervertebral disc degeneration and osteoporosis can cause damage to the cartilage endplate. Co-existence of these two factors can induce more serious damage to the endplate, which has possitive correlation with intervertebral disc degeneration. Osteoporosis plays a certain role in intervertebral disc degeneration process, and accelerates the degeneration of intervertebral disc in a specific time window.
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Objective To investigate the impact of aging and weight bearing on cartilage endplate morphology and chondrocyte apoptosis in rats. Methods The bipedal rat model (n=45) was developed by forelimb amputation and special breeding methods. The normal rats of the same age served as the control group (n=40). When the rats became 3, 6, 9, and 12 months old, 8 rats randomly selected from each group were sacrificed and paraffin-embedded mid-sagittal sections of the L4-5 spine were obtained. Sections were stained with hematoxylin and eosin and the TUNEL procedure was performed. The numbers of apoptotic cells and viable cells in the cartilage endplates of the intervertebral discs were counted, the thickness of the cartilage endplate was measured and the degree of impairment of the cartilage endplate was evaluated. Results Apoptosis first appeared in the cartilage endplate, then increased with aging and resulted in a remarkable decrease in cell density. The apoptotic rate of chondrocytes within the cartilage endplate of the bipedal rat model group was significantly higher than the control group at the 6-month time point. A statistically significant difference was observed in the bipedal rat model group between the 6-month time point and 9-month time point (P<0.05). Correlation analyses indicated that there was a highly negative correlation between the number of the viable cells of the cartilage endplate and the degree of the cartilage endplate degeneration (r=-0.97, P<0.05). Compared with the naturally aged group, the bipedal rat model group experienced more severe degeneration in the structure of the cartilage endplate, more obvious thickening of the cartilage endplate's calcified layer, and more defects in the structure of the cartilage. Conclusions Besides aging, weight bearing is probably a key factor of the increase of chondrocyte apoptosis and the degeneration of vertebral cartilage endplate.
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[Objective]This study was designed to evaluate the effects of percutaneously puncturing vertebrate adjacent to cartilage endplate and injecting pingyangmycin on lumbar intervertebral disc and cartilage endplate in New Zealand Rabbits.[Methods]Thirty-six New Zealand white rabbits were enrolled in this study.The fifth lumbar vertebmte(L_5)was injected with pingyangrnycin as experimental group,and the fourth lumbar vertebmte(L_4)injected normal sodium as control group.Six rabbits were selected randomly,then MRI and histological observation was performed in the first,second,third,fourth,Fifth week and third month after operation respectively.Moreover,the correlation analysis was performed between MRI and histological measurements for areas of the lesion in L_5.[Results]There was no obvious changes on MRI and histological examination in control group.For experimental group,there were also no obvious changes in the first two weeks after bperation.However,in the third week,it demonstrated slightly hyperintense signal on T_2WI and fat-suppression T_2WI(FS T_2WI),while FS T_1WI was hypointense signal.The signal changed more obviously in the fourth week.Histologically,the structure of vertibrates arranged disordedy,chondrocyte of endplate decreased and architecture became disorder.Anulus fibrosus and nucleus pulposus did not change.The cartilage endplate and intervertebral disc degenerated in the fifth week.Both of them degenerated more obviously in third month.There was a strong correlation between MRI and histological measurements for areas of the lesion in the fourth week(r=0.965,P＜ 0.001).[Conclusion]Degeneration of lumbar intervertebral disc and cartilage endplate in New Zealand Rabbits can be induced by percutaneously puncturing vertebrate adjacent to cartilage endplate and injecting pingyangmycin.
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STUDY DESIGN: In vitro motility assays were carried out using rat intervertebral discs (IVDs). OBJECTIVES: To demonstrate the motile properties of the cartilage endplate (CE) chondrocytes and the effect of notochordal cells on this property. LITERATURE REVIEW: Although previous in vivo studies have provided evidence for the migration of CE chondrocyte from hyaline CEs into the notochordal nucleus pulposus (NP), it is unclear if CE chondrocytes of the IVD actually have motile properties. In addition, the effect of notochordal cells on these properties has not been reported. MATERIALS AND METHODS: Notochordal cells and CE chondrocytes were harvested from three-month-old male Wistar rats and cultured separately. The motility was assayed in quadruplicate using a 48-well microchemotaxis chamber and a gelatin-coated 8-micrometer polycarbonate membrane filter. The control medium (serum-free culture medium), notochordal cells (4x, 2x, 1x and 0.5x10(6)) and concentrated conditioned medium (10-, 50-fold) where notochordal cells were cultured were loaded into the wells of the lower chamber, and CE chondrocytes were added to the wells of the upper chamber. At the end of the assays, the CE chondrocytes that migrated to the bottom side of the membrane filter were stained, counted, and compared. RESULTS: Compared with the control medium, the notochordal cells (N = 4x, 2x, 1x and 0.5x10(6)) and concentrated conditioned medium (10- and 50-fold) significantly increased the chemotactic motility of the CE chondrocytes in a number- and concentration-dependent manner (p<0.05). CONCLUSION: The CE chondrocytes of the intervertebral disc are motile, and soluble factors produced by notochordal cells induce the chemotaxis of CE chondrocytes.
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Animals , Humans , Male , Rats , Cartilage , Chemotaxis , Chondrocytes , Culture Media, Conditioned , Hyalin , Intervertebral Disc , Membranes , Notochord , Rats, WistarABSTRACT
[Objective]To find out the new method to cure the intervertebral discs degeneration by way of the eletron microscope study of the degeneration of the cartilage endplate in the circumstances of the intervertebral destabilization. [Method]To choose forty-eight white macrotia rabbits of Japan,which weighed within the range of 2.5?0.2 kg,female and male was unrestricted.These rabbits were divided into 2 groups randomly,with 21 rabbits in the contrast troup,with 27 rabbits in the experimental group.First 27 rabbits of the experimental group were destabilizated by operated on L6、7.Inj Diazepam 0.25 mg/kg,Inj Ketamine 0.02 g/kg and Inj Atropine 0.125 mg/kg was one by one injected into the rabbit through the auris vein,shearing the rabbit hair of backside waist,fixing the rabbit on operation table in face lying,using 1% Povidone Ioding to degerm the operation area.Every rabbit was incised at the backside of its waist,that incisal opening is located in the center of the intervertebral space(L6、7 space) that both side iliac crest line correspond,from the meso-ordinate direction cut about 4 cm incision,cutting open skin and subcutaneous tissue,thoroughly,exposing the spinous processes the vertebral plates and the upper-inferior articular processes,entirely segregating the muscles that cohere the spinous processes the vertebral plates and the articluar process,then excising the supraspinal ligaments and interspinal ligaments,biting off two sides the inferior articular processes of L6,in order that resulting in intervertebral destabilization,using 0.9% Inj.Sodium Chloride to washout the incisal opening,in order sewing up each layer tissues.After operation rabbits can freely move in the cages.To draw the materials from all groups after two months,four months and six months orderly.Using transmission electron microscope to observe the structure the cartilage endplate,the author should judge the degenerative course and mechanism of the cartilage endplate synthetically.[Result]The intervertebral destabilization can cause the collagen fibers degenerates from the regular and compact structure to the disorder and loose structure.[Conclusion]The intervertebral destabilization can distinctly lead to the degeneration of the cartilage endplate.
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[Objective]To study the role of nitric oxide on the degeneration of the cartilage endplate(CEP).[Method]Twenty-four New Zealand rabbits were divided into experiment and control groups.In the experiment group,the model of lumbar CEP degeneration was established by resection of all lumbar supraspinous and interspinous ligaments,excision of parts of zygapophysial joints and detachment of the posterior paravertebral muscles from lumbar vertebraes.Mechanical instability of the lumbar spine could induced the process of CEP degeneration.The X-ray examination of lumbar spine was examined by at 12,24 and 36 weeks with or without operation,respectively.Changes of the ultrastructure of CEP were also observed by scanning electron microscope(SEM) during this process,and the content of IL-1?,IL-6,TNF-? in the CEP were also detected during the periods.[Result]X-ray graph showed that the CEP calcified gradually with time increasing,and those of the experiment groups calcified more obviously than those of the control groups.The SEM showed that collagen fibers became thin,irregular and fissured and the content of proteoglycan decreased severely with the elapse of time.The changes in experiment groups were more obvious than those in control groups.The content of IL-1?,IL-6,TNF-? had a significant difference between the experiment groups and the control groups(P0.05).[Conclusion]It implies that inflammatary cytokin may play an important role in the development and progression of the degeneration of cartilage endplate.
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The aim of this study was to investigate histological composition (ratio of anulus fibrosus, cartilage endplate, and nucleus pulposus) of the herniated lumbar intervertebral disc fragments. The relative percentage of anulus fibrosus, cartilage endplate, and nucleus pulposus was examined in the herniated interverterbral disc fragments. The herniated intervertebral discs took out from the 31 patients were stained with H-E. The stained tissues were photographed, and the histological composition of the herniated intervertebral discs was analyzed after marking 3 components on the photograph with microscopic observation. The composition of the herniated lumbar intervertebral disc is 50.7% of nucleus pulposus, 41.3% of anulus fibrosus, and 8.0% of cartilage endplate. The proportion of the endplate in the herniated intervertebral disc in male was tend to be higher than that in female, and the proportion of the nucleus pulposus was tend to be decreased with aging, however, fail to reach statistical significance. This result may provide fundamental information for accessing clinical symptoms including pain in lumbar vertebral disc herniation.