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Osteoarthritis （OA）， rheumatoid arthritis （RA）， gouty arthritis （GA）， and intervertebral disc degeneration （IVDD） are the most common bone and joint-related diseases in clinical practice. They can all affect related joints， leading to joint pain， swelling， dysfunction， and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain， stiffness， and limited movement. RA is an autoimmune disease， manifested as joint pain， swelling， morning stiffness， and systemic symptoms. GA is caused by abnormal uric acid metabolism， manifested as acute arthritis， and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation， cartilage metabolism imbalance， extracellular matrix degradation， and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time， many studies have confirmed that traditional Chinese medicine （TCM） has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints， improve the pathological damage of bone and joint diseases， and relieve bone and joint pain by inhibiting pyroptosis. Therefore， this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers， TCM extracts， and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.
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Objective To evaluate the potential clinical value of T2 mapping and mDixon Quant in the diagnosis of early interver-tebral disc degeneration.Methods A total of 79 volunteers who underwent lumbar MRI examination were enrolled.All subjects were examined for 3.0T MR with T2WI,T2 mapping,and mDixon Quant while recording the condition of low back pain.The differ-ences between T2 mapping(map)value and fat fraction(FF)values of the vertebral(V)and nucleus pulposus(NP)within the Pfir-rmann Ⅰ and Pfirrmann Ⅱ intervertebral disc(grade Ⅰ 76,grade Ⅱ 87)were statistically analyzed.Receiver operating characteristic(ROC)curve analyses were performed for meaningful parameters.Results V-FF showed a mild positive correlation with degenera-tive intervertebral disc lesions,and NP-FF and NP-map values showed a mild negative correlation with lesions.There were statistically significant differences between the two groups in V-FF(P＜0.001),NP-FF(P=0.005),and NP-map(P＜0.001).Some measure-ments had statistically significant differences when different intervertebral disc segments were compared.Conclusion V-FF,NP-FF,and NP-map are associated with intervertebral disc degeneration.T2 mapping and mDixon Quant are potentially valuable as diagnostic tools to quantitatively assess early intervertebral disc degeneration and help diagnose.
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Objective To investigate the change rule of T1ρ value in the process of lumbar intervertebral disc degeneration(IVDD)based on Pfirrmann grading by Meta-analysis.Methods PubMed,EMBASE,Cochrane Library,CNKI,Wanfang Data,VIP and Sinomed were searched to collect studies on quantitative assessment of IVDD using T1ρ imaging technology.The retrieval time limit was from the establishment of the database to December 20,2022.Meta-analysis was performed using RevMan 5.4 and Stata 14.0 software.Results A total of 12 articles were included,and the numbers of Pfirrmann grade Ⅰ-Ⅴ lumbar discs were 316,1 460,769,430 and 98,respectively.T1ρ relaxation time decreased gradually with the increase of the grade of degeneration.The T1ρ values of grade Ⅰlumbar discs were significantly higher than those of grade Ⅱ lumbar discs[weighted mean difference(WMD)=14.55,95%confidence interval(CI)6.35-22.75,P<0.01],and the T1ρ values of grade Ⅱ lumbar discs were significantly higher than those of grade Ⅲlumbar discs(WMD=34.20,95%CI 27.05-41.34,P<0.01).The T1ρ values of grade Ⅲ lumbar discs were significantly higher than that of grade Ⅳ lumbar discs(WMD=22.94,95%CI 17.08-28.80,P<0.01).The T1ρ values of grade Ⅳ lumbar discs were significantly higher than that of grade Ⅴ lumbar discs(WMD=9.35,95%CI 6.81-11.89,P<0.01).Conclusion T1ρ imaging technology can objectively and quantitatively evaluate degeneration at different stages,especially sensitive to IVDD in the early and middle stages,which can provide imaging evidence for clinical diagnosis of early IVDD.
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Objective To explore the application effect of multimodal MRI in the diagnosis of lumbar intervertebral disc degeneration.Methods A total of 78 patients with lumbar intervertebral disc degeneration treated conservatively were retrospectively selected.The patients underwent sagittal T2WI,axial T2WI sequence and sagittal synthetic MRI scanning and post-processing to generate T1,T2 and proton density(PD)mapping quantitative sequences by GE Signa Pioneer 3.0T MR machine.The T1,T2 and PD values of the anterior and posterior annulus fibrosus and nucleus pulposus of L1-L2 to L5-S1 lumbar intervertebral disc were measured.The Pfirrmann grade,visual analogue scale(VAS)and Oswestry disability index(ODI)scale of each intervertebral disc were evaluated.The T1,T2,PD,VAS and ODI of patients with different Pfirrmann grades were compared.Pearson linear analysis was used to analyze the relationship between T1,T2,PD and VAS,ODI.Spearman rank correlation method was used to analyze the relationship between T1,T2,PD and Pfirrmann.Logistic regression analysis was used to analyze the evaluation value of T1,T2 and PD in Pfirrmann.Results With the increase of Pfirrmann grade,the T1,T2 and PD values of patients decreased,while the VAS score and ODI increased(P<0.05).The T1,T2 and PD values were negatively correlated with VAS score,ODI and Pfirrmann grade(P<0.05).Logistic regression analysis showed that T1,T2 and PD values had good evaluation values for Pfirrmann grade(P<0.05).Conclusion Multimodal MRI can effectively evaluate the Pfirrmann grade,pain and lumbar function of lumbar intervertebral disc degeneration,which can be used to help determine the diagnosis.
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BACKGROUND:Intervertebral disc degeneration is clinically considered to be the main cause of low back pain,but due to the unclear pathogenesis of intervertebral disc degeneration,there is still a lack of effective means to delay the progression of the disease.Single-cell RNA sequencing technology can amplify and sequence mRNA at the single-cell level,reveal the gene expression intensity of a single cell,discover different cell subsets in tissues according to the heterogeneity of cells,study the pathogenesis of intervertebral disc degeneration at the molecular level,and provide a new theoretical basis for its early diagnosis and treatment. OBJECTIVE:To introduce the basic principles of single-cell RNA sequencing technology and review the research progress of single-cell RNA sequencing technology in intervertebral disc degeneration in recent years. METHODS:A computer was used to search PubMed,Web of Science,CNKI and WanFang databases for the literature published from 2012 to 2022.Key words were"single-cell RNA sequencing,intervertebral disc degeneration,sequencing Technology"in Chinese and English.Duplicate,poor-quality and irrelevant articles were excluded;a total of 70 articles were eventually included. RESULTS AND CONCLUSION:(1)We identified new cell subsets such as homeostatic chondrocytes,hypertrophy chondrocyte-like nucleus pulposus cells and fibrous nucleus pulposus cells,identified the marker genes and transcription factors of these cell subsets,and described the functions,differentiation paths and cell fate of these cell subsets during the development and progression of intervertebral disc degeneration,and proposed the concept of progenitor nucleus pulposus cells.A cell subpopulation with progenitor nucleus pulposus cells properties was identified and its effectiveness in treating intervertebral disc degeneration was verified in mice.(2)Fibro chondrocyte-like annulus fibrosus cells and annulus fibrosus stem cells with both cartilage and fiber properties were identified,and a new type of composite hydrogel was prepared by combining fibrous cartilage inducers silk fibroin and hyaluronic acid in vitro.Experiments in mice demonstrated that this hydrogel could repair both annulus fibrosus tissue and cartilage matrix,and was remarkably effective in the treatment of intervertebral disc degeneration.(3)Regulatory chondrocytes were found in endplate cartilage.Two distinct fates in the progression of intervertebral disc degeneration were analyzed and the differential genes in the two fates were identified.Intercellular communication analysis indicated that regulatory chondrocytes interact with endothelial cells to promote angiogenesis.(4)Immune cells such as macrophages,T cells,myeloid progenitor cells and neutrophils were identified in the degenerated intervertebral disc tissues,demonstrating the existence of immune response during intervertebral disc degeneration.It was found that apolipoprotein induced the polarization of macrophages M1 and M2 subtypes,and this polarization process affected the activity of progenitor nucleus pulposus cells by amplifying the inflammatory response through the MIF signaling pathway.
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BACKGROUND:MicroRNA(miRNA)levels are closely related to cell apoptosis and proliferation,extracellular matrix metabolism and inflammatory response in intervertebral disc cells.However,the specific role of miR-142-3p in lumbar intervertebral disc degeneration remains unclear. OBJECTIVE:To investigate the correlation between the expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in nucleus pulposus tissue and degree of human lumbar intervertebral disc degeneration. METHODS:A total of 82 patients with lumbar intervertebral disc degenerative diseases in Suzhou Ninth People's Hospital from January 2020 to March 2022 were collected as the study subjects,all of whom underwent MRI examination before operation.According to the Videman classification,the patients were divided into mild degeneration group(n=36),moderate degeneration group(n=26)and severe degeneration group(n=20).Eighty-two specimens of the nucleus pulposus were obtained.The mRNA expression of miRNA-142-3p as well as the mRNA and protein expression of mixed lineage kinase 3,interleukin-1β,type I collagen,type II collagen in nucleus pulposus tissue were detected by qPCR and western blot assay.The correlation between the degree of human lumbar intervertebral disc degeneration and the expression levels of miRNA-142-3p,mixed lineage kinase 3,and interleukin-1β was also assessed using the Spearman correlation coefficient method.Thirty adult Sprague-Dawley rats were divided into sham-operated group(executed after puncturing skin and muscle only),mild degeneration group(executed 1 week after puncturing Co7/8 segments)and severe degeneration group(executed 2 weeks after puncturing Co7/8 segments),with 10 rats in each group.After that,we detected the protein expression of mixed lineage kinase 3 and interleukin-1β as well as the gene expression of miRNA-142-3p,mixed lineage kinase 3 and interleukin-1β in the nucleus pulposus tissue. RESULTS AND CONCLUSION:In human nucleus pulposus tissue,the miRNA-142-3p expression ranked from high to low as follows:mild degeneration group>moderate degeneration group>severe degeneration group(P<0.05);the gene and protein expression of mixed lineage kinase 3 and interleukin-1β from low to high was as follows:mild degeneration group<moderate degeneration group<severe degeneration group(P<0.05);the gene and protein expression of type I collagen from low to high was as follows:mild degeneration group<moderate degeneration group<severe degeneration group(P<0.05),and the gene and protein expression of type I collagen from high to low was as follows:mild degeneration group>moderate degeneration group>severe degeneration group(P<0.05).Spearman correlation analysis showed that the degree of disc degeneration was negatively correlated with miRNA-142-3p expression(P<0.05)and positively correlated with mixed lineage kinase 3 and interleukin-1β expression(P<0.05).In rat nucleus pulposus tissue,compared with the sham-operated group,the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was elevated in the mild degeneration group(P<0.05)while miRNA-142-3p expression was decreased(P<0.05);compared with the mild degeneration group,the expression of mixed lineage kinase 3 and interleukin-1β gene and protein was increased in the severe degeneration group(P<0.05)while miRNA-142-3p expression was decreased(P<0.05).To conclude,the degree of human lumbar intervertebral disc degeneration is negatively correlated with miRNA-142-3p expression and positively correlated with mixed lineage kinase 3 and interleukin-1β expression in nucleus pulposus tissue.
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BACKGROUND:Intervertebral disc degeneration is the basis of spinal degenerative diseases;however,there is no effective treatment. OBJECTIVE:To investigate whether sinomenine can inhibit interleukin-1β-induced apoptosis in nucleus pulposus cells and its molecular mechanism. METHODS:Rat nucleus pulposus cells were cultured in vitro by trypsin combined with type II collagenase digestion,and the cell growth curve was plotted.An appropriate sinomenine concentration was determined using the cell counting kit-8 kit.Nucleus pulposus cells were divided into control group,sinomenine group,interleukin-1β group,sinomenine+interleukin-1β group,zinc protoporphyrin group,zinc protoporphyrin+sinomenine group,zinc protoporphyrin+interleukin-1β group,and sinomenine+zinc protoporphyrin+interleukin-1β group.Proliferative activity,reactive oxygen species content,apoptosis rate,and heme oxygenase-1 expression in nucleus pulposus cells were detected. RESULTS AND CONCLUSION:The rat nucleus pulposus cells cultured in vitro were polygonal,triangular,and short wedge-shaped,and the cell growth showed an"S"curve.The cells grew slowly in the first 3 days of culture,rapidly in 4-6 days,and slowly again in 7-8 days.The cells then entered the"platform stage"where the number of cells no longer increased.The proliferative activity of myeloid cells showed no significant changes when the concentration of sinomenine was≤80 μmol/L(P>0.05).Interleukin-1β significantly reduced the proliferative activity of nucleus pulposus cells,increased the content of reactive oxygen species and led to apoptosis(P<0.01).Sinomenine intervention not only promoted heme oxygenase-1 expression(P<0.05)but also inhibited interleukin-1β-induced decrease in proliferative activity and increase in reactive oxygen species content and apoptosis rate in nucleus pulposus cells(P<0.05).These effects could be reversed by zinc protoporphyrin(P<0.01).
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BACKGROUND:Salvianolic acid B can inhibit cell damage induced by H2O2,effectively remove excess reactive oxygen species,and exert antioxidant properties.It has been used in the treatment of many diseases.However,there are relatively few studies on the role and mechanism of salvianolic acid B in intervertebral disc degeneration. OBJECTIVE:To observe the effect and mechanism of salvianolic acid B on oxidative stress-induced intervertebral disc degeneration by using gelatin methacryloyl hydrogel as a carrier through the in vitro cell experiment and the in vivo animal experiment. METHODS:The gelatin methacryloyl hydrogel(drug-loaded hydrogel)loaded with salvianolic acid B was prepared.(1)In vitro cell experiment:The lumbar nucleus pulposus cells of adult SD rats were isolated and extracted,and passage 3 nucleus pulposus cells were selected and divided into groups:Group A was added complete medium.In group B,a complete medium containing H2O2 was added.Group C was inoculated on methylacrylylated gelatin hydrogel and added with a complete medium containing H2O2.Group D was inoculated on methyl acrylyl gelatin hydrogel loaded with salvianolic acid B and added into a complete medium containing H2O2.The E group was inoculated on the methylacrylyl gelatin hydrogel loaded with salvianolic acid B,and the complete medium containing H2O2 and the complete medium containing TLR4 signaling pathway inhibitor were added.Cell proliferation,oxidative stress,inflammatory response,gene expression of cell matrix-associated proteins and the protein expression of TLR4/nuclear factor-kB signaling pathway were detected.(2)Animal in vivo experiment:Sixty adult SD rats were randomly divided into normal group,acupuncture group,acupuncture + salvianolic acid group,acupuncture + hydrogel group and acupuncture + loading potion gel group,with 12 rats in each group.The last four groups were treated with acupuncture to establish models of intervertebral disc degeneration and then injected with normal saline,salvianolic acid B solution,non-drug loaded gel and drug-loaded gel in turn.Imaging examination and pathological observation were performed 4 weeks after surgery. RESULTS AND CONCLUSION:(1)In vitro cell experiment:Compared with group A,the cell proliferation was decreased;the oxidative stress reaction and inflammation reaction were enhanced;the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was increased in group B(P<0.05),and the synthesis of extracellular matrix(type Ⅱ collagen,proteoglycan)was decreased(P<0.05).The protein expression of the TLR4/nuclear factor-kB signaling pathway was increased(P<0.05).Compared with group B,the cell proliferation of groups D and E was increased,the oxidative stress response and inflammatory response were weakened,and the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was decreased(P<0.05),and the synthesis of extracellular matrix was increased(P<0.05).The protein expression of TLR4/nuclear factor-kB signaling pathway was decreased(P<0.05),and the effect was more significant in group E.(2)Animal in vivo experiment:4 weeks after surgery,intervertebral disc height index,index of MRI and pathological and histological grading of the intervertebral disc had improved significantly in the acupuncture+drug-loaded hydrogel group,and simply injecting hydrogel or salvianolic acid B solution can to a certain extent improve the intervertebral disc degeneration,but they are not as good as the injection of the drug-loaded hydrogel.(3)It is concluded that gelatin methacryloyl hydrogel loaded with salvianolic acid B can inhibit oxidative stress and inflammation in the degenerated intervertebral disc tissue,inhibit the degradation of extracellular matrix,and alleviate the process of intervertebral disc degeneration,which may be accomplished by inhibiting the TLR4/nuclear factor-kB signaling pathway.
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BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.
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BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.
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BACKGROUND:Lumbar fixed-point rotation operation needs collaborative operation of the doctor's hands,and outputs rotation and thumb thrust.Lumbar disc herniation can be treated through disc displacement and adjusting stress distribution.However,the mechanical effects of thumb thrust and the biomechanical effects of loading direction on manipulative effects remain unclear. OBJECTIVE:To compare the biomechanical difference of lumbar fixed-point rotation manipulation for treating lumbar disc herniation under different thrust directions. METHODS:The L3-5 normal three-dimensional finite element model was constructed and validity was verified.According to the intervertebral disc degeneration Pfirrmann grade,intervertebral disc degeneration was simulated by modifying the L4/5 intervertebral space height,the volume of the nucleus pulposus,as well as the material parameters of the annulus fibrosus,nucleus pulposus,and ligament.Finally,the pathological model of L4/5 moderate disc degeneration with left para-central herniation was constructed,and then the pathological models were used as research objects.Simulation technique:spinning to the right;taking the condition on changing the direction of the thumb thrust to establish three modes of operation(M1:thumb push to the left;M2:thumb push to the right;M3:no thrust push).The protrusion displacement and the disc stress,and the stress and strain of the facet joint cartilage were compared in the three operating modes. RESULTS AND CONCLUSION:(1)Maximum displacement value of L4/5 disc herniation:displacement was 2.672 3 mm for M1,1.156 1 mm for M2,1.826 4 mm for M3,M1＞M3＞M2.(2)The maximum Von Mises stress of L4/5 discs was 1.846 7 MPa for M1,0.419 0 MPa for M2,and 1.257 9 MPa for M3,M1＞M3＞M2.(3)L4/5 bilateral small cartilage produced different degrees of contact stress changes:It was 0.485 5 MPa for M1,0.026 7 MPa for M2,and 0.441 4 MPa for M3,M1＞M3＞M2.Right cartilage contact force was 0.000 5 MPa for M1,0.025 9 MPa for M2,and 0.001 3 MPa for M3,M2＞M3＞M1;the left greater than the right,M1 had the highest value;cartilage strain was consistent with contact stress changes.(4)Different operation modes will have some biomechanical influences on the diseased intervertebral disc and accessory structure.The M1 operation mode can maximize the displacement of protrusion,disc stress and left joint cartilage contact,which can better promote disc displacement,balance stress distribution and reduce facet joint disorder,so the operation is better.
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BACKGROUND:Wnt signaling pathway is overexpressed in degenerative intervertebral discs,and inhibition of its expression can delay the process of intervertebral disc degeneration.Therefore,Wnt signaling pathway is closely related to intervertebral disc degeneration. OBJECTIVE:To summarize the relationship between Wnt signaling pathway and intervertebral disc,especially the specific role and influence of Wnt signaling pathway in intervertebral disc degeneration. METHODS:The first author took"intervertebral disc,Wnt,cell proliferation,cell senescence,cell apoptosis,extracellular matrix"as the English search terms.PubMed,Web of science and OVID LWWSpringerlink were searched for articles published from 2000 to January 2023,and articles related to Wnt signaling pathway and disc degeneration were consulted.Totally 54 articles were reviewed by reading,collating and preserving. RESULTS AND CONCLUSION:(1)During intervertebral disc formation in embryos,Wnt signaling pathway is overexpressed,which is involved in intervertebral disc formation and promotes posterior extension of notochord.(2)During intervertebral disc degeneration,Wnt signaling pathway can inhibit cell proliferation by stagnating cell cycle,increase the expression of age-related proteins and promote cell aging by participating in oxidative stress,and participate in cell apoptosis by regulation of long non-coding RNA.(3)Wnt signaling pathway can also decrease extracellular matrix related protein synthesis,promote extracellular matrix degradation and accelerate intervertebral disc degeneration.(4)Wnt signaling pathway can promote cell regeneration by activating as early intervertebral disc formation signal and participate in inducing stem cells to differentiate into intervertebral disc cells to repair damaged intervertebral disc.For example,Wnt signaling pathway can induce stem cells from cartilage endplate cells to migrate and transform to intervertebral disc.
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BACKGROUND:Intervertebral disc degeneration is one of the most common underlying factors causing low back pain.Recent studies have shown that melatonin has a positive effect on alleviating intervertebral disc degeneration.However,the underlying mechanism of melatonin remains to be elucidated. OBJECTIVE:To explore the biological effect and potential mechanism of melatonin in inhibiting hydrogen peroxide(H2O2)-induced injury of human nucleus pulposus cells. METHODS:Human nucleus pulposus cells insolated from degenerative intervertebral disc were cultured in vitro.Cell proliferation and the optimal intervention concentration of melatonin and H2O2 were detected by cell counting kit-8.The Human nucleus pulposus cells treated with H2O2 were used as a model group;the cells treated with H2O2 and intervened with melatonin were used as a melatonin group;the cells cultured in simple medium were used as a control group.The reactive oxygen species levels were detected by 2',7'-dichlorofluorescin diacetate(DCFH-DA),the expression levels of BAX and Caspase3 were detected by immunofluorescence,and the mRNA expression levels of BAX,BCL-2,Casepase3,PI3K and AKT were detected using the real-time fluorescent quantitative reverse transcription PCR. RESULTS AND CONCLUSION:The results of cell counting kit-8 experiment showed that the optimal intervention concentration of H2O2 was 400 μmol/L and the optimal intervention concentration of melatonin was 5 μmol/L.The reactive oxygen species level in the melatonin group was significantly lower than that in the model group.The average fluorescence intensity of BAX and Caspase3 in the melatonin group was significantly lower than that in the model group.The mRNA expressions of BAX and Caspase3 in the melatonin group were lower than those in the model group,while the mRNA expression of Bcl-2 was increased.In addition,the mRNA expressions of PI3K and AKT were also higher in the melatonin group compared with the model group.To conclude,melatonin may protect human nucleus pulposus cells from H2O2-induced oxidative damage through the PI3K/AKT signaling pathway.
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BACKGROUND:Oxidative stress plays a critical role in intervertebral disc degeneration.As a reducing material with good biocompatibility,black phosphorus quantum dots have the potential to resist oxidative stress and retard intervertebral disc degeneration.OBJECTIVE:To evaluate the effect of black phosphorus quantum dots on scavenging reactive oxygen species in the microenvironment of an intervertebral disc through in vivo and in vitro experiments,and further explore the role of black phosphorus quantum dots in Nrf2/ARE pathway and intervertebral disc inflammation.METHODS:Black phosphorus quantum dots were prepared by a liquid exfoliation technique.(1)In vitro experiment:The nucleus pulposus cells of SD rats were isolated and extracted,and the passages 2-4 nucleus pulposus cells were cocultured with different solutions,including F12-DMEM medium(blank group),black phosphorus quantum dot solution,hydrogen peroxide solution,hydrogen peroxide+black phosphorus quantum dot solution,hydrogen peroxide+black phosphorus quantum dot+Nrf2 specific inhibitor ML385 solution.Cell live/dead staining and intracellular reactive oxygen species,mitochondrial membrane potential and western blot assay were performed respectively.(2)In vivo experiment:Thirty SD rats were randomly divided into sham operation,puncture and puncture + black phosphorus groups,with 10 rats in each group.A Co7-10 intervertebral disc degeneration model was established using intervertebral disc puncture in the puncture group and the puncture+black phosphorus group.Black phosphorus quantum dot solution was injected in the intervertebral disc after a puncture in the puncture+black phosphorus group.The intervertebral disc tissue imaging and histological staining were evaluated at 4 and 8 weeks after surgery.RESULTS AND CONCLUSION:(1)In vitro experiment:Live/dead staining revealed that the black phosphorus quantum dots had good biocompatibility,were non-toxic to cells,and had a protective effect on nucleus pulposus cells under oxidative stress.Intracellular reactive oxygen species and JC-1 fluorescent probes showed that black phosphorus quantum dots could regulate the reduction of mitochondrial membrane potential caused by oxidative stress in nucleus pulposus cells and protected cells from hydrogen peroxidation-induced intracellular oxidative stress.Western blot analysis showed that compared with the blank group,the protein expressions of Nrf2,heme oxygenase 1,quinone oxidoreductase and type Ⅱ collagen were decreased in the hydrogen peroxide group(P<0.05),while the protein expressions of tumor necrosis factor α,interleukin 1β,matrix metalloproteinase 13 and p65 were increased(P<0.05).The addition of black phosphorus quantum dots could reverse the inhibitory effect of hydrogen peroxide on the Nrf2 pathway and reduce the inflammatory response caused by oxidative stress,but NrF2-specific inhibitors could cancel this effect.(2)In vivo experiment:X-ray and MRI demonstrated that at 4 and 8 weeks after surgery,the intervertebral disc height and water content of nucleus pulposus in the puncture group were lower than those in the sham operation group(P<0.05),and the intervertebral disc height and water content of nucleus pulposus in the puncture+black phosphorus group were higher than those in the puncture group(P<0.05).Histological staining exhibited that the degree of intervertebral disc degeneration in the puncture+black phosphorus group was less than that in the puncture group,and the expression of heme oxygenase 1 protein was higher than that in the puncture+black phosphorus group.(3)Our results have indicated that black phosphorus quantum dots can exert an antioxidant effect and delay intervertebral disc degeneration by regulating Nrf2/ARE pathway.
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BACKGROUND:Platelet-rich plasma can promote the repair and regeneration of intervertebral disc tissue.Percutaneous transforaminal endoscopic discectomy is widely used in the treatment of lumbar disc herniation.In recent years,more and more scholars have focused on the combined treatment of lumbar disc herniation with the two techniques in order to achieve a better patient prognosis. OBJECTIVE:To investigate the clinical safety and effectiveness of percutaneous transforaminal endoscopic discectomy combined with platelet-rich plasma in the treatment of lumbar disc herniation. METHODS:The clinical data of 58 patients with lumbar disc herniation who met the inclusion and exclusion criteria at Sixth Medical Center of PLA General Hospital from June 2017 to May 2018 were retrospectively analyzed.Among them,29 patients underwent percutaneous transforaminal endoscopic discectomy combined with platelet-rich plasma(observation group),and the remaining 29 patients underwent percutaneous transforaminal endoscopic discectomy only(control group).Visual Analogue Scale score for back and leg pain,lumbar JOA score,and Oswestry Disability Index were evaluated preoperatively,at 3,6,and 12 months postoperatively,and at the last follow-up.Intervertebral space height,nucleus pulposus to cerebrospinal fluid signal strength ratio,and intervertebral disc Pfirrmann grading were measured preoperatively,at 6 and 12 months postoperatively,and at the last follow-up.The modified MacNab criteria were used to assess excellent and good rate of curative effect at the last follow-up. RESULTS AND CONCLUSION:(1)The Visual Analogue Scale score for back and leg pain,JOA score,and Oswestry Disability Index of the two groups postoperatively were significantly improved compared with those preoperatively(P<0.05).Visual Analogue Scale score and Oswestry Disability Index were lower in the observation group than those in the control group at 3 and 6 months postoperatively(P<0.05).The JOA score was higher in the observation group than that in the control group at 3 and 6 months postoperatively(P<0.05).(2)The nucleus pulposus to cerebrospinal fluid signal strength ratio was higher in the observation group than that in the control group at the last follow-up(P<0.05).Pfirrmann grading of the intervertebral discs was better in the observation group than that in the control group(P<0.05).The excellent and good rate was 93%in the observation group and 83%in the control group,and the difference was not statistically significant(P>0.05).(3)These findings indicate that percutaneous transforaminal endoscopic discectomy combined with platelet-rich plasma in the treatment of lumbar disc herniation has satisfactory clinical efficacy and can delay the degeneration of the intervertebral disc to a certain extent.
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BACKGROUND:Intervertebral disk degeneration is a pathological change caused by a series of complex molecular mechanisms that result in the aging and damage of intervertebral discs,ultimately leading to severe clinical symptoms.Traditional Chinese medicine has unique advantages in the treatment of intervertebral disk degeneration due to its low cost,non-addictive nature,multi-target effects,minimally toxic and side effects,and high patient acceptance. OBJECTIVE:To review the latest research results of traditional Chinese medicine monomer intervention-related signaling pathways in the treatment of intervertebral disk degeneration,describe and analyze the action mechanism of traditional Chinese medicine monomer on intervertebral disk degeneration,and provide a new approach and theoretical basis for future basic research and clinical treatment. METHODS:The first author searched for relevant literature from January 2018 to February 2023 in CNKI,PubMed,VIP,and WanFang using the search terms"intervertebral disc,signal pathway".The articles that did not meet the criteria were excluded after preliminary screening of the titles and abstracts.Finally,72 articles were selected for review and analysis. RESULTS AND CONCLUSION:Traditional Chinese medicine monomers can regulate multiple classical signaling pathways such as Wnt/β-catenin,PI3K/Akt,mTOR,NF-κB,and MAPK.They achieve this by regulating oxidative stress,adjusting the expression of pro/anti-apoptotic proteins in cells,stimulating cellular autophagy function,reducing stimulation of cell inflammatory factors,increasing the expression of extracellular matrix markers,reducing the production of matrix-degrading enzymes,maintaining the synthesis and stability of extracellular matrix,inducing differentiation of mesenchymal stem cells in the nucleus pulposus into nucleus pulposus cells,promoting endogenous repair and reconstruction,controlling apoptosis and aging of nucleus pulposus cells,and increasing the activity of nucleus pulposus cells.These actions improve the microenvironment within the intervertebral disc,maintain the normal physiological function of the intervertebral disc,and delay intervertebral disc degeneration.
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BACKGROUND:Early diagnosis and treatment of intervertebral disc degeneration is particularly important.Pyroptosis of nucleus pulposus cells plays an important role in the early process of intervertebral disc degeneration,but the role of pyroptosis-related molecules of nucleus pulposus cells in early intervertebral disc degeneration and related molecular markers are still unclear. OBJECTIVE:To explore the diagnostic and therapeutic value of differentially expressed genes related to pyroptosis during intervertebral disc degeneration. METHODS:Public datasets of the GEO database were integrated for differential analysis,and intersected with 33 pyroptosis-related genes previously reported.Using Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes,pathway enrichment analysis was performed in genes related to pyroptosis during intervertebral disc degeneration.Enrichment analysis of the intervertebral disc degeneration dataset was conducted using gene set enrichment analysis.To construct the immune cell spectrum in intervertebral disc degeneration samples,the correlation between the differentially expressed pyroptosis-related genes and immune cells was analyzed.Protein interaction networks were built.Screening of the Hub gene to identify key genes associated with intervertebral disc degeneration in protein interaction networks.The receiver operating characteristic curve of the differentially expressed pyroptosis-related genes was plotted,and the area under the curve was calculated.The clinical diagnostic value of target genes was explored.qRT-PCR was applied to verify the difference in the expression of pyroptosis-related genes between normal human nucleus pulposus cells and degenerated human nucleus pulposus cells with intervertebral discs. RESULTS AND CONCLUSION:(1)4426 differentially expressed genes associated with intervertebral disc degeneration were obtained,and 14 differentially expressed pyroptosis-related genes were obtained after the intersection.(2)Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed important enrichment pathways,mainly related to inflammation,cell cycle,infection and NOD-like receptor pathway.Gene set enrichment analysis showed that pathways such as amino acid metabolism and P53 transcription regulation were significantly enriched in patients with intervertebral disc degeneration.Immune infiltration analysis suggested that the occurrence and development of intervertebral disc degeneration were closely related to immune cells.(3)A total of five Hub genes were screened,namely IL1-β,Caspase-1,AIM2,Caspase-5,and NLRC4.(4)Acquisition and identification of key biomarkers for intervertebral disc degeneration:After intersecting the two datasets of GEO with the pyroptosis-related gene,it was found that NLRP3 had significant expression differences,and the receiver operating characteristic curve showed that NLRP3 had clinical diagnostic significance.(5)qRT-PCR showed that the expression of Hub genes such as IL1-β,Caspase-5 and NLRC4 was significantly increased in the nucleus pulposus cells of intervertebral disc degeneration(P<0.05),and there was no difference in Caspase-1,AIM2 and NLRP3 expression(P>0.05).(6)It is suggested that cell pyroptosis plays an important mechanism in the occurrence and development of intervertebral disc degeneration,among which pyroptosis-related molecules NLRP3,IL1-β,Caspase-5 and NLRC4 have early diagnosis and treatment value.
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BACKGROUND:Semaphone 3A(Sema3A)is an important neurovascular growth inhibitor.It is not clear how Sema3A is involved in the pathogenesis of discogenic low back pain.Exploring the potential mechanism of Sema3A in intervertebral disc degeneration can provide a new target and theoretical basis for the prevention and treatment of discogenic low back pain. OBJECTIVE:To explore the mechanism of interleukin-1β inhibiting the expression of Sema3A by activating the nuclear factor-κB signaling pathway to induce intervertebral disc degeneration in rats. METHODS:RT-qPCR was used to detect the expression of Sema3A mRNA in normal and degenerative human nucleus pulposus tissues.Nucleus pulposus cells of Sprague-Dawley rats were isolated,cultured,and passaged to the 3rd generation.Then,passage 3 cells were divided into three groups:the blank control group was routinely cultured for 48 hours,the degeneration group was intervened with 10 ng/mL interleukin 1β for 48 hours,and the degeneration+inhibitor group was treated by 5 μmol/L nuclear factor-κB signaling pathway-specific inhibitor BAY11-7082 for 1 hour,followed by interleukin-1β for 48 hours.At the end of the intervention,cell viability was detected by cell counting kit-8,cell apoptosis was detected by Annexin V/FITC staining,mRNA expression of cellular matrix,vascular and neural markers and Sema3A was detected by RT-qPCR,and protein expression of marker proteins,p65 and p-p65 was detected by western blot. RESULTS AND CONCLUSION:RT-qPCR assay showed that the expression of Sema3A mRNA was lower in degenerative human nucleus pulposus tissue than in normal human nucleus pulposus tissue(P＜0.05).Compared with the blank control group,the nucleus pulposus cell viability decreased and the apoptotic rate increased in the degeneration group(P＜0.05);compared with the degeneration group,the nucleus pulposus cell viability increased and the apoptotic rate decreased in the degeneration + inhibitor group(P＜0.05).Compared with the blank control group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),while mRNA expression of CD31 and neurofilament 200 was increased(P＜0.05).Compared with the degeneration group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05)and mRNA expression of CD31 and neurofilament 200 decreased(P＜0.05).Compared with the blank control group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),and the protein expression of CD31,neurofilament protein 200,p65,and p-p65 was elevated(P＜0.05);compared with the degeneration group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05),and protein expression of CD31,neurofilament 200,p65,and p-p65 was decreased(P＜0.05).To conclude,interleukin-1β does inhibit the expression of Sema3A by activating the nuclear factor-κB signaling pathway,which can also increase the degradation of extracellular matrix,promote the innervation and angiogenesis in degenerative intervertebral disc,and may be one of potential factors that contribute to intervertebral disc degeneration and discogenic low back pain.
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BACKGROUND:Stem cell transplantation is a new way to prevent and cure intervertebral disc degeneration.However,whether the transplanted stem cells can survive,proliferate,differentiate,and restore the function of nucleus pulposus cells after transplantation,is the key and difficult point to overcome. OBJECTIVE:To explore the effects of Bushenhuoxue decoction on survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells. METHODS:A Transwell chamber was used to construct a co-culture model of human adipose-derived stem cells and human degenerative nucleus pulposus cells.The experiment was divided into control group,model group,drug-containing serum group,and drug-free serum group.Except for the control group,the co-culture system of other groups was treated with 50 μmol/L tert-butyl hydrogen peroxide for 24 hours.The drug-containing serum group and drug-free serum group were treated with DMEM low-glucose complete culture medium containing drug-containing serum of Bushenhuoxue decoction or drug-free serum with 20％volume fraction for 48 hours.The sublayer adipose-derived stem cells were taken.Toluidine blue staining was used to detect proteoglycan synthesis levels.Real-time PCR method was used to detect mRNA expression of type Ⅱ collagen,proteoglycan and SRY-box transcription factor 9.The protein expression of SOX9 was detected by western blot assay.Lactate dehydrogenase assay was used to detect cytotoxicity.Flow cytometry was used to detect reactive oxygen species,and β-galactosidase staining was used to detect cell senescence. RESULTS AND CONCLUSION:(1)Compared with the control group,the proportion of necrotic cells in the model group increased;toluidine blue staining became lighter,and the expression levels of type Ⅱ collagen,proteoglycan,SOX9 mRNA and SOX9 protein decreased(P<0.05).Compared with the model group,the drug-containing serum of Bushenhuoxue decoction could significantly reduce cell injury and promote the expression of type Ⅱ collagen,proteoglycan,SOX9 mRNA,and SOX9 protein(P<0.05),but the improvement in the drug-free serum group was not significant(P>0.05).(2)Compared with the control group,the contents of cytotoxicity,reactive oxygen species,and cell senescence in the model group were significantly increased.Compared with the model group,the microenvironment of the coculture system was significantly improved by drug-containing serum of Bushenhuoxue decoction(P<0.05),while drug-free serum had no significant effect on the microenvironment of the co-culture system(P>0.05).(3)The results show that Bushenhuoxue decoction can promote the survival,proliferation,and nucleus pulposus-like differentiation of adipose-derived stem cells.
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BACKGROUND:Nucleus pulposus cell apoptosis is the main pathological basis for intervertebral disc degeneration,and inflammation and peroxidation are important factors leading to apoptosis in the nucleus pulposus.Studies have shown that matrine has antioxidant,senescent,inflammatory and apoptotic effects,and may be a potential drug for the treatment of disc degeneration. OBJECTIVE:To investigate the effect of matrine on apoptosis of nucleus pulposus cells in rats with intervertebral disc degeneration by regulating the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway. METHODS:(1)Nucleus pulposus cells of rats at a logarithmic phase were randomly separated into a control group,a model group,a low-dose matrine group,a high-dose matrine group,an empty group,and a high-dose matrine+cGAS overexpression group.Except for the control group,cell models of intervertebral disc degeneration were established in the other groups through oxygen-glucose deprivation.At the same time of modeling,the low-dose and high-dose groups were treated with 0.4 and 0.8 mmol/L matrine,respectively,and the empty group was transfected with the empty plasmid,while the high-dose+cGAS overexpression group was treated with 0.8 mmol/L matrine with the transfection of the cGAS overexpression plasmid.After 24 hours of treatment,cell activity and apoptosis,intracellular levels of reactive oxygen species,superoxide dismutase,tumor necrosis factor α and interleukin 1β,and intracellular expression of apoptotic proteins and cGAS-STING pathway proteins were detected.(2)Sixty Sprague-Dawley rats were randomized into six groups(n=10 per group):control group,model group,low-dose matrine group,high-dose matrine group,empty group,and high-dose+cGAS overexpression group.After 12 weeks of modeling,60 and 120 mg/kg matrine were given by gavage in the low-dose and high-dose matrine groups,respectively(once a day),and the empty plasmid was injected into the tail vein in the empty group(2 times/week),while the high-dose+cGAS overexpression group was given 120 mg/kg matrine by gavage and injected with cGAS overexpression plasmid to the tail vein.Treatment in each group was given consecutively for 3 weeks.Samples were taken after drug administration and assayed for apoptosis,levels of reactive oxygen species,superoxide dismutase,tumor necrosis factor α and interleukin 1β,as well as apoptotic protein and cGAS-STING pathway protein expression. RESULTS AND CONCLUSION:Compared with the control group,in the model group,cell activity and superoxide dismutase levels were decreased(P<0.05),and apoptosis rate,levels of reactive oxygen species,tumor necrosis factor α and interleukin 1β,and the expression of cGAS,STING,cleaved caspase-3 and Bax proteins were elevated(P<0.05).Matrine dose-dependently ameliorated the above changes in each index due to cellular modeling(P<0.05),whereas cGAS overexpression partially antagonized the ameliorative effect of high-dose matrine.Similar results to the in vitro cellular experiments were obtained in animal experiments.These results indicate that matrine could inhibit inflammation and oxidative stress by blocking the cGAS-STING signaling,which in turn attenuates apoptosis and elevates the activity of nucleus pulposus cells in rats with intervertebral disc degeneration.