The Artificial Disc Nucleus and Other Strategies for Replacement of the Nucleus Pulposus:Past,Present and Future Designs for an Emerging Surgical Solution

Nucleus Pulposus(NP)Replacement is a developing surgical methodology for the treatment of pathology related to degeneration of intervertebral discs(IVDs).This article provides necessary context regarding the patholo-gies treated with this technology,the biomechanical structure and function of the IVD,and the procedures this technology aims to replace.Primarily,it provides an overview and discussion of commercial and experimental preformed and in situ curing prosthesis designs reported in the scientific literature and summarizes the results of biomechanical and clinical studies evaluating their efficacy.Contextual and updated information on the most recent research into NP replacement with novel hydrogel and tissue engineering(TE)strategies is described.Replacement of the NP allows for potential improvement in the treatment of degenerative spinal pathologies through minimally invasive surgical techniques.

Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus Cells In Vitro

To find a new source of seed cells for constructing tissue-engineered intervertebral disc, nucleus pulposus （NP） cells and mesenchymal stem cells （MSCs） were isolated from New Zealand white rabbits. The nucleus pulposus cells population was fluorescence-ladled and co-cultured with MSCs with or without direct contact. Morphological changes were observed every 12 h. Semi-quantitaive reverse transcriptase-polymerase chain reaction was performed to assess the expression levels of Sox-9, aggreacan and type Ⅱ collagen every 24 h after the co-culture. MSCs treated with direct contact rounded up and presented a ring-like appearance. The expression of marker genes was significantly increased when cells were co-cultured with direct contact for 24 h. No significant change was found after coculture without direct contact. Co-culture of NP cells and MSCs with direct contact is a reliable method for generating large amount of NP cells used for cell-based tissue engineering therapy.

Normal and Degenerated Rabbit Nucleus Pulposus Cells in in vitro Cultures: A Biological Comparison

This study examined the biological characteristics of normal and degenerated rabbit nucleus pulposus （NP） cells in vitro in order to provide seed cells for intervertebral disc （IVD） tissue engineering. A total of 8 adult New Zealand white rabbits underwent annulus puncture to establish models ofintervertebral disc degeneration （IDD）. Four weeks later, normal and degenerated NP cells were obtained. Cell morphology was observed by light and electron microscopy. Cell viability was measured by MTT assay. Cell cycle and expression of extracellular matrix （ECM）-related genes （aggrecan and type II col- lagen） were determined by using flow cytometry and RT-PCR respectively. The growth curve of normal NP cells showed that the cells at passage 4 tended to slowly grow on the fifth day of culture. The density of normal NP cells at passages 5 to 7 was significantly less than that of the first-passage cells 2 or 3 days after seeding （P〈0.05）. The degenerated NP cells at passage 3 showed slow growth at 4th day. After 5 passages, the degenerated NP cells assumed stagnant growth and the growth seemed to stop at passage 7. The MTT assay revealed that for both normal and degenerated NP cells, the absorbance （.4） value at passages 4-7 was obviously decreased as compared with that at passage 1 （P〈0.05）. Cell cycle analysis showed that the proportion of normal NP cells at G1 phase was 65.4%-3.5%, significantly lower than that of degenerated NP cells at the same cell cycle phase With the value being 77.6%-4.8%. The degen- erated NP cells were predominantly arrested at Gt phase and failed to enter S phase. The expression of type II collagen and aggrecan was significantly decreased with passaging. It was concluded that normal NP cells possessed good viability and proliferative capacity by the third passage, and they could secrete large amounts of ECM within this period. The normal NP cells may serve as seed cells for IVD tissue engineering.

CERVICAL STABILITY AFTER CUTTING-ASPIRATION OF NUCLEUS PULPOSUS

The effects of cutting-aspiration of nucleus pulposus on the momements of the cervical spine in flexion,extension and lateral bending with fresh cervical spine specimens were tested by means of contacting measement with the dial indicators when loaded with the electronic universal testing machine.The results showed:(1) Cutting-aspiration of nucleus pulposus only removed part of the nucleus pulposus,which was consistent with the clinical observation;(2)The ranges or motion(ROMs) of the operative segment had not increased in direction of flexion,extension and lateral bending after cutting-aspiration of nucleus pulposus:(3)After nucleotomy,the ROMs corresponding upon the operative segment apparently increased in flexion and extension,but had no change in lateral bending;(4)Hemilaminectomy of cervical spine which was an operation or partial removal of the ligamentum flavum and the lamina only had little afrection on the cervical stability. The biomechanical data can not only demonstrate the reliability of percutaneous dlscectomy,but also present a new enlightement for the clinical therapy of cervical disc herniation with spinal canal stenosis.

The role of transcriptional factor brachyury in the development and repair of nucleus pulposus

Transcription factor Brachyury,a protein containing 435 amino acids,has been widely investigated and reported in notochord differentiation and nucleus pulposus development.The crucial functions and underlying mechanisms by Brachyury are discussed in this paper,which suggests Brachyury can be developed into a potential novel target for the therapy of intervertebral disc degeneration.

Nucleus Pulposus Cells from Calcified Discs Promote the Degradation of the Extracellular Matrix through Upregulation of the GATA3 Expression

Objective Disc calcification is strongly associated with disc degeneration;however,the underlying mechanisms driving its pathogenesis are poorly understood.This study aimed to provide a gene expression profile of nucleus pulposus cells(NPCs)from calcified discs,and clarify the potential mechanism in disc degeneration.Methods Primary NPCs were isolated from calcified and control discs(CAL-NPC and CON-NPC),respectively.The proliferation and extracellular matrix(ECM)metabolism capacities of the cells were evaluated using MTT and Western blotting,respectively.RNA sequencing was used to identify differentially expressed genes(DEGs)in the CAL-NPCs.The biological functions of the DEGs were analyzed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network.The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated.Results The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs.In total,375 DEGs were identified in the CAL-NPCs.The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways.GATA-binding protein 3(GATA3)with the highest verified levels was selected for further studies.Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function,while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes.Conclusion This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.

Effect of Yaobitong capsule on histomorphology of dorsal root ganglion and on expression of p38mark phosphorylation in autologous nucleus pulposus transplantation model of rats

Objective:To discuss the effect of Yaobitong capsule on histomorphology of dorsal root ganglion and on expression of p38 MARK phosphorylation in autologous nucleus pulposus transplantation model of rats.Methods:A total of 60 SD rats were randomly divided into the blank group,model group and Yaobitong capsule group,with 20 rats in each group.The animal model of autologous nucleus pulposus transplantation around the lumbar nerve root was built.Three days after the modeling,rats were given the drugs for the first time,while rats in the model group were given the equivalent normal saline.After 30 d of continuous administration,samples were collected from rats.HE staining was performed on the dorsal root ganglion of L4 and L5 spinal cord of rats in each group and the expression of p38 MARK phosphorylation was measured.All data were treated with the statistical analysis.Results:The histological examination showed that the histomorphology of dorsal root ganglion in the Yaobitong capsule group was more significantly improved than the one in the model group,while the results of western blot showed that Yaobitong capsule could significandy inhibit the level of p38 MAPK phosphorylation of dorsal root ganglion cells.Conclusions:Yaobitong capsule can improve the symptoms and nerve radiculopathy of autologous nucleus pulposus transplantation of rats and its mechanism may be associated with its inhibiting effect on the level of p38 MAPK phosphorylation.

Pilot biomechanical design of biomaterials for artificial nucleus prosthesis using 3D finite-element modeling

Pilot biomechanical design of biomaterials for artificial nucleus prosthesiswas carried out based on the 3D finite-element method. Two 3D models of lumbar intervertebral discrespectively with a real human nucleus and with the nucleus removed were developed and validatedusing published experimental and clinical data. Then the models with a stainless steel nucleusprosthesis implanted and with polymer nucleus prostheses of various properties implanted were usedfor the 3D finite-element biomechanical analysis. All the above simulation and analysis were carriedout for the L4/L5 disc under a human worst--daily compression load of 2000 N. The results show thatthe polymer materials with Young's modulus of elasticity E = 0.1-100 MPa and Poisson's ratio v=0.35-0.5 are suitable to produce artificial nucleus prosthesis in view of biomechanicalconsideration.

Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration(IVDD).Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc.This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1(TGF-β1)(T-NNPs)onto the surface of methacrylic acid gelatin anhydride microspheres(GM)via amide bonds.The nanoparticle-microsphere complex(GM@T-NNPs)sustained the long-term release of T-NNPs with excellent cell-like functions,effectively bound to pro-inflammatory cytokines,and improved the release kinetics of TGF-β1,maintaining a 36 day-acting release.GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro,downregulated the expression of inflammatory factors and matrix metalloproteinase,and upregulated the expression of collagen-II and aggrecan.GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model.The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

Transplantation of gene-modified nucleus pulposus cells reverses rabbit intervertebral disc degeneration

Background Intervertebral disc degeneration is the main cause of low back pain. The purpose of this study was to explore potential methods for reversing the degeneration of lumbar intervertebral discs by transplantation of gene-modified nucleus pulposus cells into rabbit degenerative lumbar intervertebral discs after transfecting rabbit nucleus pulposus cells with adeno-associated virus 2 （AAV2）-mediated connective tissue growth factor （CTGF） and tissue inhibitor of metalloproteinases 1 （TIMP1） genes in vitro. Methods Computer tomography （CT）-guided percutaneous annulus fibrosus injury was performed to build degenerative lumbar intervertebral disc models in 60 New Zealand white rabbits, rAAV2-CTGF-IRES-TIMPI-transfected rabbit nucleus pulposus cells were transplanted into degenerative lumbar intervertebral discs （transplantation group）, phosphate-buffered saline （PBS） was injected into degenerative lumbar intervertebral discs （degeneration control group） and normal lumbar intervertebral discs served as a blank control group. After 6, 10 and 14 weeks, the disc height index （DHI） and signal intensity in intervertebral discs were observed by X-ray and magnetic resonance imaging （MRI） analysis The expression of CTGF and TIMP1 in nucleus pulposus tissue was determined by Western blotting analysis, the synthesis efficiency of proteoglycan was determined by a 35S-sulfate incorporation assay, and the mRNA expression of type II collagen and proteoglycan was detected by RT-PCR. Results MRI confirmed that degenerative intervertebral discs appeared two weeks after percutaneous puncture. Transgenic nucleus pulposus cell transplantation could retard the rapid deterioration of the DHI. MRI indicated that degenerative intervertebral discs were relieved in the transplantation group compared with the degeneration control group. The expression of collagen II mRNA and proteoglycan mRNA was significantly higher in the transplantation group and the blank control group compared with the degeneration control group （P 〈0.05）. Conclusions CT-guided percutaneous puncture can successfully build rabbit degenerative intervertebral disc models. Both CTGF and TIMPl-transfected cell transplantation helps to maintain disc height, and promotes the biosynthesis of tvDe II collaQen and proteoalvcan in intervertebral discs, reversinq the de（：ieneration of intervertebral discs.

Autologous nucleus pulposus transplantation to lumbar 5 dorsal root ganglion after epineurium discission in rats： a modified model of non-compressive lumbar herniated intervertebral disc

Background Nucleus pulposus of intervertebral discs has proinflammatory characteristics that play a key role in neuropathic pain in lumbar herniated intervertebral disc. One of the most commonly used animal models （the traditional model） of non-compressive lumbar herniated intervertebral disc is created by L4-L5 hemilaminectomy and the application of autologous nucleus pulposus to cover the left L4 and L5 nerve roots in rats. However, such procedures have the disadvantages of excessive trauma and low success rate. We proposed a modified model of non-compressive lumbar herniated intervertebral disc in which only the left L5 dorsal root ganglion is exposed and transplanted with autologous nucleus pulposus following incision of epineurium. We aimed to compare the modified model with the traditional one with regard to trauma and success rate. Methods Thirty Sprague-Dawley male rats were randomized into three groups： sham operation group （n=6）, traditional group （n=12）, and modified group （n=12）. The amount of blood loss and operative time for each group were analyzed. The paw withdrawal threshold of the left hind limb to mechanical stimuli and paw withdrawal latency to heat stimuli were examined from the day before surgery to day 35 after surgery. Results Compared with the traditional group, the modified group had shorter operative time, smaller amount of blood loss, and higher success rate （91.7% versus 58.3%, P 〈0.05）. There was no decrease in paw withdrawal latency in any group. The sham operation group had no decrease in postoperative paw withdrawal threshold, whereas the modified and traditional groups had significant reduction in paw withdrawal threshold after surgery （mechanical hyperalgesia）. Conclusions Transplantation of nucleus pulposus onto the L5 dorsal root ganglion following incision of epineurium in rats established an improved animal model of non-compressive lumbar herniated intervertebral disc with less trauma and more stable pain ethology.

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Objective： To construct a recombinant adenovirus vector-carrying human growth and differentiation factor-5 （GDF-5） gene, investigate the biological effects of adenovirus-mediated GDF-5 （Ad-GDF-5） on extracellular matrix （ECM） expression in human degenerative disc nucleus pulposus （NP） cells, and explore a candidate gene therapy method for intervertebral disc degeneration （IDD）. Methods： Human NP cells of a degenerative disc were isolated, cultured, and infected with Ad-GDF-5 using the AdEasy-1 adenovirus vector system. On Days 3, 7, 14, and 21, the contents of the sulfated glycosaminoglycan （sGAG）, deoxyribonucleic acid （DNA） and hydroxyproline （Hyp）, synthesis of proteoglycan and collagen II, gene expression of collagen II and aggrecan, and NP cell proliferation were assessed. Results： The adenovirus was an effective vehicle for gene delivery with prolonged expression of GDF-5. Biochemical analysis revealed increased sGAG and Hyp contents in human NP cells infected by Ad-GDF-5 whereas there was no conspicuous change in basal medium （BM） or Ad-green fluorescent protein （GFP） groups. Only cells in the Ad-GDF-5 group promoted the production of ECM, as demonstrated by the secretion of proteoglycan and up-regulation of collagen II and aggrecan at both protein and mRNA levels. The NP cell proliferation was significantly promoted. Conclusions： The data suggest that Ad-GDF-5 gene therapy is a potential treatment for IDD, which restores the functions of degenerative intervertebral disc through enhancing the ECM production of human NP ceils.

Evaluation of CD24 as a marker to rapidly define the mesenchymal stem cell phenotype and its differentiation in human nucleus pulposus

Background Recent studies have indicated that human nucleus pulposus contain mesenchymal stem cells （NP-MSCs）. However, the immunophenotypic variation of NP-MSCs in vitro was unclear. The present study was conducted to address the immunophenotypic variation of mesenchymal stem cells in nucleus pulposus under continuous proliferation in vitro and show the difference between mesenchymal stem cells and nucleus pulposus cell. Methods Tissue samples were obtained from thoracolumbar burst fracture patients and degenerative disc disease patients who underwent discectomy and fusion procedures. Flow cytometric and laser scanning confocal microscope （LSCM） were used to detect the variation of mesenchymal stem cells in nucleus pulposus which were expressing CD105 and CD24 in condition with or without transforming growth factor [31 （TGF-131）. Results More than 90% of the analyzed primary cells of mesenchymal stem cells in nucleus pulposus fulfilled the general immunophenotyping criteria for MSCs, such as CD44, CD105 and CD29, but the marker of mature NP cells characterized as CD24 was negative. In continuous cultures, the proportion of mesenchymal stem cells which were expressing CD44, CD105 and CD29 in nucleus pulposus gradually decreased. The mesenchymal stem cells in nucleus pulposus cells were positive for CD105 and CD29, with slight positivity for CD44. The CD24 expression gradually increased in proliferation. Bi- parametric flow cytometry and laser scanning confocal microscopy confirmed the presence of cells which were expressing CD105 and CD24 independently, and only a small part of cells expressed both CD105 and CD24 simultaneously. TGF-{31 could stimulate mesenchymal stem cells in nucleus pulposus to express CD24. Conclusions Non-degenerative and degenerative NP contains mesechymal stem cells. The variation of CD24 can be used as a marker to identify the NP-MSCs differentiation into NP-like cells.

An esterase-responsive ibuprofen nano-micelle pre-modified embryo derived nucleus pulposus progenitor cells promote the regeneration of intervertebral disc degeneration

Stem cell-based transplantation is a promising therapeutic approach for intervertebral disc degeneration(IDD).Current limitations of stem cells include with their insufficient cell source,poor proliferation capacity,low nucleus pulposus(NP)-specific differentiation potential,and inability to avoid pyroptosis caused by the acidic IDD microenvironment after transplantation.To address these challenges,embryo-derived long-term expandable nucleus pulposus progenitor cells(NPPCs)and esterase-responsive ibuprofen nano-micelles(PEG-PIB)were prepared for synergistic transplantation.In this study,we propose a biomaterial pre-modification cell strategy;the PEG-PIB were endocytosed to pre-modify the NPPCs with adaptability in harsh IDD microenvironment through inhibiting pyroptosis.The results indicated that the PEG-PIB pre-modified NPPCs exhibited inhibition of pyroptosis in vitro;their further synergistic transplantation yielded effective functional recovery,histological regeneration,and inhibition of pyroptosis during IDD regeneration.Herein,we offer a novel biomaterial pre-modification cell strategy for synergistic transplantation with promising therapeutic effects in IDD regeneration.

Effects of degenerative autologous nucleus pulposus on the lumbar sympathetic trunk: Sympathetic inflammation in rats

Objective: We have reported the presence of discogenic visceral pain secondary to anterior herniation of the lumbar disc. The aim of this study was to observe the inflammatory response of the sympathetic trunk to an autologous degenerative nucleus pulposus(NP) injection under fluoroscopy. Methods: A total of 72 rats were used. In 24 rats,the autologous NP suspension was injected into the right sympathetic trunk. Next,food intake and body weight of each rat were monitored for 14 days. Fourteen days after the injection,the right lumbar sympathetic trunk was harvested for histological assessment,and protein levels of IL-1 β,IL-6,and TNF-α were quantified via ELISA. Results: In the NP-treated group,endoneural hyperemia and intensive infiltration of inflammatory cells could be identified in sections of the sympathetic trunk by the hematoxylin and eosin(H&E) stain. Meanwhile,elevated concentrations of IL-1 β,IL-6,and TNF-α were determined in the sympathetic trunk of the NP group as compared to that of the na?ve and control groups,which indicated the development of an inflammatory response. Furthermore,food intake and body weight of rats in the NP group decreased significantly. Conclusions: The results indicated that an inflammatory response in the sympathetic trunk can be caused by anterior herniation of the lumbar disc,which can generate a sympathetic inflammatory pain response.

Gua Sha attenuates thermal hyperalgesia and decreases proinflammatory cytokine expression in serum in rats with lumbar disc herniation induced by autologous nucleus pulposus

OBJECTIVE: To investigate the analgesic effect of Gua Sha and its underlying mechanism in rats with noncompressive lumbar disk herniation induced by autologous nucleus pulposus.METHODS: A rat model of noncompressive lumbar disk herniation was established and rats were randomly divided into model group, sham group, and Gua Sha group(24 in each group). Gua Sha was performed from the 5 th day after the surgery, once every other day, 3 times for a course of treatment,and totally 3 courses. The thermal withdrawal latency was evaluated using the intelligent hot plate one day before the surgery, and on days 4(the day before the treatment), 10(the end of the firstcourse), 16(the end of the second course) and 22(the end of the third course). On days 4, 10, 16 and22, six rats in each group were picked randomly and their blood samples were drawn to assess the expression of interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-alpha(TNF-α).RESULTS: Compared to rats in the sham group, the application of nucleus pulposus to right L5 dorsal root ganglion induced prolonged thermal hyperalgesia, and up-regulated the expression of IL-1β,IL-6 and TNF-α in serum(P < 0.01). The therapy of Gua Sha attenuated thermal hyperalgesia potently,inhibited the expression of IL-1β, IL-6 and TNF-α in a time-dependent manner(P < 0.01). There were no significant differences in the thermal withdrawal latency and the expression of inflammatory cytokines between the sham and Gua Sha groups at the end of the treatment(P > 0.01).CONCLUSION: The current study showed that Gua Sha might alleviate thermal hyperalgesia in rats with lumbar disc herniation induced by autologous nucleus pulposus via inhibiting the expression of proinflammatory cytokins.

颈椎椎间盘人工髓核置换术的生物力学评价

目的 :对颈椎椎间盘实施人工髓核置换术并进行生物力学评价 ,为临床应用提供理论依据。方法 :取 6具新鲜人尸体颈椎标本 (C2 ～T1 ) ,制成四种脊柱功能单位 (FSU)的试验模型 :正常颈椎 ,椎间盘髓核全切 ,人工髓核植入及椎间植骨。分别对其进行生物力学测试 ,记录不同运动状态下脊柱节段运动范围 (ROM)的改变情况。并摄片了解人工髓核植入前后脊柱试件影像学的变化。结果 :与髓核切除组比较 ,人工髓核植入或椎间植骨后 ,颈椎节段活动明显减少 (P <0 .0 1)。人工髓核植入组与椎间植骨组相比较 ,节段活动差异无显著性 (P <0 .0 5 )。动态影像学资料显示 ,人工髓核置入后 ,椎间隙高度和脊柱生理曲度都得以恢复。结论 :颈椎椎间盘人工髓核的植入能较好地恢复椎间盘的解剖结构 ,有助于脊椎生理曲线的恢复 ,从而在一定程度上增加失稳脊柱节段的稳定性。

Comparison of microendoscopic discectomy and open discectomy for single-segment lumbar disc herniation

BACKGROUND Lumbar disc herniation is a common disease.Endoscopic treatment may have more advantages than traditional surgery.AIM To compare the clinical efficacy and safety of microendoscopic discectomy(MED)and open discectomy with lamina nucleus enucleation in the treatment of singlesegment lumbar intervertebral disc herniation.METHODS Ninety-six patients who were operated at our hospital were selected for this study.Patients with single-segment lumbar disc herniation were admitted to the hospital from March 2018 to March 2019 and were randomly divided into the observation group and the control group with 48 cases in each group.The former group underwent lumbar discectomy and the latter underwent laparotomy and nucleus pulpectomy.Surgical effects were compared between the two groups.RESULTS In terms of surgical indicators,the observation group had a longer operation time,shorter postoperative bedtime and hospital stay,less intraoperative blood loss,and smaller incision length than the control group(P<0.05).The excellent recovery rate did not differ significantly between the observation group(93.75%)and the control group(91.67%).Visual analogue scale pain scores were significantly lower in the observation group than in the control group at 1 d,3 d,1 mo,and 6 mo after surgery(P<0.05).The incidence of complications was significantly lower in the observation group than in the control group(6.25%vs 22.92%,P<0.05).CONCLUSION Both MED and open discectomy can effectively improve single-segment lumbar disc herniation,but MED is associated with less trauma,less bleeding,and a lower incidence of complications.

腰椎椎间盘人工髓核置换(附20例随访)

目的 :观察腰椎间盘人工髓核置换的效果。方法和结果 :为了减少腰椎间盘突出症手术后的后遗症 ,我们设计了人工髓核置换的手术 ,临床已进行了 2 0例 ,除一例掉出来外 ,19例随访 2～ 7年 ,疗效优良 ,能够维持椎体间术前高度。髓核假体是椭圆形用硅橡胶制成。通过流行的后路椎间盘摘除手术进路 ,利用特制的注入器将假体注入椎间盘中央。因纤维环上切口小 ,假体恢复圆形后比切口大 ,不易掉出来 ,一例掉出来的原因和防止方法作了介绍。文中从生物力学和解剖生理学方面讨论了此手术的价值和恢复此椎间盘功能的可能性。此手术不扩大切口 ,不延长手术时间 ,不增加病人痛苦 ,不影响原来椎间盘摘除术疗效 ,易为术者和病者接受 ,有推广应用价值。

Specific Inhibitory Protein Dkk-1 Blocking Wnt/β-catenin Signaling Pathway Improve Protectives Effect on the Extracellular Matrix

The present study examined the role of Wnt/β-catenin signaling pathway in the degeneration of nucleus pulposus cells and the protective effect of DKK1 on nucleus pulposus cells. The model of nucleus pulposus cell degeneration was induced by intra-disc injection of TNF-α, and the expression of β-catenin protein was detected by Western blotting. The cultured rabbit nucleus pulposus cells were divided into 4 groups. In group A, the cells were cultured with normal medium and served as control group. In group B, the cells were cultured with TNF-α and acted as degeneration group. In group C, the cells were cultured with TNF-α and transfected with Adv-eGFP and was used as fluorescence control group. In group D, the cells were cultured with TNF-α and transfected with Adv-hDKK1-eGFP, serving as intervention group. The expression of typeⅡcollagen, proteoglycan, β-catenin, and MMP-13 in each group was detected by immunocytochemistry and RT-PCR. The result showed that TNF-α increased the expression of β-catenin and MMP-13, and significantly inhibited the synthesis of type Ⅱ collagen and proteoglycan, which resulted in the degeneration of nucleus pulposus cells. This effect could be obviously reversed by DKK1. We are led to concluded that TNF-α could activate the Wnt/β-catenin signaling pathway, and increase the expression of MMP-13, thereby resulting in disc degeneration. Specifically blocking Wnt/β-catenin signaling pathway by DKK-1 could protect the normal metabolism of intervertebral disc tissue. The Wnt pathway plays an important role in the progression of the intervertebral disc degeneration.