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Sirt6 deficiency promotes senescence and age-associated intervertebral disc degeneration in mice
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作者 Pranay Ramteke Bahiyah Watson +8 位作者 Mallory Toci Victoria A.Tran Shira Johnston Maria Tsingas Ruteja A.Barve Ramkrishna Mitra Richard F.Loeser John A.Collins Makarand V.Risbud 《Bone Research》 2025年第4期925-938,共14页
Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recen... Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration. 展开更多
关键词 intervertebral disc degeneration skeletal tissue autophagy conditional del intervertebral disc SIRT disc degeneration SENESCENCE
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The mitochondrial E3 ligase MAPL SUMOylates Drp1 to facilitate mitochondrial fission in intervertebral disc degeneration
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作者 Zhidi Lin Xiao Lu +9 位作者 Guangyu Xu Jian Song Hongli Wang Xinlei Xia Feizhou Lu Jianyuan Jiang Wei Zhu Zuochong Yu Xiaosheng Ma Fei Zou 《Bone Research》 2025年第5期1239-1251,共13页
Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulp... Intervertebral disc degeneration(IVDD)is the primary contributor to a range of spinal diseases.Dynamin-related protein 1(Drp1)-mediated mitochondrial fission has recently been identified as a new cause of nucleus pulposus cell(NPC)death and IVDD,but the underlying mechanisms remain unclear.Although the effects of Drp1 phosphorylation in IVDD have been studied,it is currently unknown if small ubiquitin-like modifications(SUMOylation)of Drp1 regulate IVDD.This study aimed to investigate the functions and mechanisms of mitochondria-anchored protein ligase(MAPL),a mitochondrial SUMO E3 ligase,during IVDD progression.The expression of genes related to SUMOylation and mitochondrial dynamics in TNF-α-stimulated NPCs was analysed via RNA sequencing. 展开更多
关键词 intervertebral disc degeneration ivdd spinal diseasesdynamin related mitochondrial e ligase mapl intervertebral disc degeneration mitochondrial fission SUMOYLATION DRP
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Chaperone-mediated autophagy directs a dual mechanism to balance premature senescence and senolysis to prevent intervertebral disc degeneration
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作者 Zhangrong Cheng Haiyang Gao +8 位作者 Pengzhi Shi Anran Zhang Xianglong Chen Yuhang Chen Weikang Gan Kangcheng Zhao Shuai Li Cao Yang Yukun Zhang 《Bone Research》 2025年第4期1028-1046,共19页
Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-med... Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies. 展开更多
关键词 lamp knockout intervertebral Disc Degeneration Dyrk Glutamine Metabolism SENESCENCE Senescence Associated Secretory Phenotype intervertebral disc degeneration idd nucleus pulposus cells npc plays
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Reprogramming to restore youthful epigenetics of senescent nucleus pulposus cells for mitigating intervertebral disc degeneration and alleviating low back pain
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作者 Wenzheng Ma Wantao Wang +9 位作者 Lei Zhao Jinghao Fan Lei Liu Lin Huang Baogan Peng Jianru Wang Baoshan Xu Hongmei Liu Decheng Wu Zhaomin Zheng 《Bone Research》 2025年第3期716-730,共15页
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment... Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD. 展开更多
关键词 youthful epigenetics senescent nucleus pulposus cells intervertebral disc degeneration REPROGRAMMING intervertebral disc degeneration ivdd low back pain nucleus pulposus cells npcs partially reprogram reinstate youthful epigenetics
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Therapeutic strategies for intervertebral disc degeneration:Extracellular vesicles and microRNAs derived from mesenchymal stem cells
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作者 Young-Ju Lim Min-Soo Seo +1 位作者 Sangbum Park Gun Woo Lee 《World Journal of Stem Cells》 2025年第7期55-66,共12页
Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and in... Intervertebral disc degeneration(IDD)results from an imbalance within the intervertebral disc,leading to alterations in extracellular matrix composition,loss of nucleus pulposus cells,increased oxidative stress,and inflammatory cascade.While IDD naturally progresses with age,some factors such as mechanical trauma,lifestyle choices,and genetic abnormalities can elevate the risk of symptomatic disease progression.Current treatments,including pharmacological and surgical interventions,fail to halt disease progression or restore IDD function.Although biological therapies have been evaluated,their effectiveness in reversing long-term disc degeneration remains inconsistent.Mesenchymal stem cellbased therapies have demonstrated potential for IDD regeneration but are hindered by biological limitations,ethical issues,etc.To date,mesenchymal stem cell-derived extracellular vesicles(EVs)have emerged as promising therapeutic agents for regeneration and anti-inflammation.Their therapeutic effects are attributed to several mechanisms,such as the induction of regenerative phenotype,apoptosis mitigation,and immunomodulation.In addition,the abundance of microRNAs within EVs play a crucial role in modulating the disc degeneration.Due to the problems in clinical use,however,the efficiency of the EVs should be overcome further by optimizing cell culture conditions,engineering them to deliver drugs and targeting molecules,etc. 展开更多
关键词 intervertebral disc DEGENERATION REGENERATION Therapy Stem cell Extracellular vesicles MicroRNA SECRETOME
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Role of neurogenic inflammation in intervertebral disc degeneration
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作者 Bao-Gan Peng Yong-Chao Li Liang Yang 《World Journal of Orthopedics》 2025年第1期24-39,共16页
In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports t... In healthy intervertebral discs(IVDs),nerves and blood vessels are present only in the outer annulus fibrosus,while in degenerative IVDs,a large amount of nerve and blood vessel tissue grows inward.Evidence supports that neurogenic inflammation produced by neuropeptides such as substance P and calcitonin gene related peptide released by the nociceptive nerve fibers innervating the IVDs plays a crucial role in the process of IVD degeneration.Recently,non-neuronal cells,including IVD cells and infiltrating immune cells,have emerged as important players in neurogenic inflammation.IVD cells and infiltrating immune cells express functional receptors for neuropeptides through which they receive signals from the nervous system.In return,IVD cells and immune cells produce neuropeptides and nerve growth factor,which stimulate nerve fibers.This communication generates a positive bidirectional feedback loop that can enhance the inflammatory response of the IVD.Recently emerging transient receptor potential channels have been recognized as contributors to neurogenic inflammation in the degenerative IVDs.These findings suggest that neurogenic inflammation involves complex pathophysiological interactions between sensory nerves and multiple cell types in the degenerative IVDs.Clarifying the mechanism of neurogenic inflammation in IVD degeneration may provide in-depth understanding of the pathology of discogenic low back pain. 展开更多
关键词 intervertebral disc degeneration Discogenic low back pain Neurogenic inflammation NEUROPEPTIDES NEUROTROPHINS Transient receptor potential channels
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Stem cell therapy for intervertebral disc degeneration:Clinical progress with exosomes and gene vectors
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作者 Zhi-Peng Li Han Li +13 位作者 Yu-Hua Ruan Peng Wang Meng-Ting Zhu Wei-Ping Fu Rui-Bo Wang Xiao-Dong Tang Qi Zhang Sen-Li Li He Yin Cheng-Jin Li Yi-Gong Tian Rui-Ning Han Yao-Bin Wang Chang-Jiang Zhang 《World Journal of Stem Cells》 2025年第4期20-35,共16页
Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture... Intervertebral disc degeneration is a leading cause of lower back pain and is characterized by pathological processes such as nucleus pulposus cell apoptosis,extracellular matrix imbalance,and annulus fibrosus rupture.These pathological changes result in disc height loss and functional decline,potentially leading to disc herniation.This comprehensive review aimed to address the current challenges in intervertebral disc degeneration treatment by evaluating the regenerative potential of stem cell-based therapies,with a particular focus on emerging technologies such as exosomes and gene vector systems.Through mechanisms such as differentiation,paracrine effects,and immunomodulation,stem cells facilitate extracellular matrix repair and reduce nucleus pulposus cell apoptosis.Despite recent advancements,clinical applications are hindered by challenges such as hypoxic disc environments and immune rejection.By analyzing recent preclinical and clinical findings,this review provided insights into optimizing stem cell therapy to overcome these obstacles and highlighted future directions in the field. 展开更多
关键词 EXOSOMES Extracellular matrix repair Gene vector system Hypoxic environment intervertebral disc degeneration Mesenchymal stem cells Regenerative medicine Stem cell therapy
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Fundamentals of intervertebral disc degeneration and related discogenic pain
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作者 Bao-Gan Peng 《World Journal of Orthopedics》 2025年第1期18-23,共6页
Lumbar intervertebral disc degeneration is thought to be the main cause of low back pain,although the mechanisms by which it occurs and leads to pain remain unclear.In healthy adult discs,vessels and nerves are presen... Lumbar intervertebral disc degeneration is thought to be the main cause of low back pain,although the mechanisms by which it occurs and leads to pain remain unclear.In healthy adult discs,vessels and nerves are present only in the outer layer of the annulus fibrosus and in the bony endplate.Animal models,and histological and biomechanical studies have shown that annulus tear or endplate injury is the initiating factor for painful disc degeneration.Injury to the disc triggers a local inflammatory repair response that activates nociceptors and promotes the synthesis of neuropeptides such as substance P and calcitonin generelated peptide,by dorsal root ganglion neurons.These neuropeptides are transported to injured discs and act as pro-inflammatory molecules,promoting the production of an“inflammatory soup”by inducing vasodilatation and plasma extravasation as well as by promoting the release of chemical mediators from disc cells and infiltrating immune cells,causing neurogenic inflammation that leads to progressive disc degeneration and discogenic pain. 展开更多
关键词 intervertebral disc degeneration Discogenic low back pain Neurogenic inflammation NEUROPEPTIDES Substance P Calcitonin gene-related peptide
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3D bioprinted chondrogenic gelatin methacrylate-poly(ethylene glycol)diacrylate composite scaffolds for intervertebral disc restoration
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作者 Maria D Astudillo Potes Maryam Tilton +5 位作者 Indranath Mitra Xifeng Liu Babak Dashtdar Emily T Camilleri Benjamin D Elder Lichun Lu 《International Journal of Extreme Manufacturing》 2025年第1期610-621,共12页
Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative appr... Degenerative spine pathologies,including intervertebral disc(IVD)degeneration,present a significant healthcare challenge due to their association with chronic pain and disability.This study explores an innovative approach to IVD regeneration utilizing 3D bioprinting technology,specifically visible light-based digital light processing,to fabricate tissue scaffolds that closely mimic the native architecture of the IVD.Utilizing a hybrid bioink composed of gelatin methacrylate(GelMA)and poly(ethylene glycol)diacrylate(PEGDA)at a 10%concentration,we achieved enhanced printing fidelity and mechanical properties suitable for load-bearing applications such as the IVD.Preconditioning rat bone marrow-derived mesenchymal stem cell spheroids with chondrogenic media before incorporating them into the GelMA-PEGDA scaffold further promoted the regenerative capabilities of this system.Our findings demonstrate that this bioprinted scaffold not only supports cell viability and integration but also contributes to the restoration of disc height in a rat caudal disc model without inducing adverse inflammatory responses.The study underscores the potential of combining advanced bioprinting techniques and cell preconditioning strategies to develop effective treatments for IVD degeneration and other musculoskeletal disorders,highlighting the need for further research into the dynamic interplay between cellular migration and the hydrogel matrix. 展开更多
关键词 intervertebral disc regeneration 3D bioprinting gelatin-based hydrogels mesenchymal stem cell spheroids tissue engineering
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A mouse coccygeal intervertebral disc degeneration model with tail-looping constructed using a suturing method
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作者 Wei Xie Zemao Huang +9 位作者 Ziyang Huang Deqing Luo Zhangxin Chen Li Xie Lingqi Zhu Hui Liu Kejian Lian Paolo Alberton Denitsa Docheva Dasheng Lin 《Animal Models and Experimental Medicine》 2025年第9期1645-1655,共11页
Backgroud:Intervertebral disc degeneration(IDD)is one of the common degenerative diseases.Due to ethical constraints,it is difficult to obtain sufficient research on humans,so the use of an animal model of IDD is very... Backgroud:Intervertebral disc degeneration(IDD)is one of the common degenerative diseases.Due to ethical constraints,it is difficult to obtain sufficient research on humans,so the use of an animal model of IDD is very important to clarify the pathogenesis and treatment mechanism of the disease.Methods:In this study,thirty 2-month-old mice were selected for operation to establish a coccygeal IDD model.The distal tail portion of the tail(beyond the 17th coccygeal vertebra)and a small piece of skin above the 8th coccygeal vertebra were excised,and the two incisions were brought together after flexion,and secured with sutures.The heights and signal intensities of the intervertebral discs(IVDs)were assessed using microcomputed tomography(μCT)and magnetic resonance imaging(MRI)at 0,6,12 weeks postoperatively.The overall tissue morphology,cell distribution and density,and extracellular matrix of the IVDs were also assessed using Hematoxylin and Eosin(HE),Safranin O-Fast Green and immunohistochemical staining.Results:All mice in the experimental group survived after the operation,and there were no complications such as wound infection,tail necrosis and suture shedding.The experimental results demonstrated that the suturing method can successfully initiate IDD.Different severity levels of IDD can be induced by controlling the bending angle of the IVDs within the tail loop;however,for consistency,histologic and imaging results should be obtained at the same bending angle and looping period.Conclusions:This IDD model is an effective method for studying the etiology and treatment of degenerative IVD disease. 展开更多
关键词 animal model intervertebral disc degeneration mechanical stress MICE
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D‑mannose alleviates intervertebral disc degeneration through glutamine metabolism
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作者 Zheng-Lin Dong Xin Jiao +8 位作者 Zeng-Guang Wang Kai Yuan Yi-Qi Yang Yao Wang Yun-Tao Li Tian-Chang Wang Tian-You Kan Jian Wang Hai-Rong Tao 《Military Medical Research》 2025年第3期313-338,共26页
Background:Intervertebral disc degeneration(IVDD)is a multifaceted condition characterized by heterogeneity,wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus(NP)cells... Background:Intervertebral disc degeneration(IVDD)is a multifaceted condition characterized by heterogeneity,wherein the balance between catabolism and anabolism in the extracellular matrix of nucleus pulposus(NP)cells plays a central role.Presently,the available treatments primarily focus on relieving symptoms associated with IVDD without offering an effective cure targeting its underlying pathophysiological processes.D-mannose(referred to as mannose)has demonstrated anti-catabolic properties in various diseases.Nevertheless,its therapeutic potential in IVDD has yet to be explored.Methods:The study began with optimizing the mannose concentration for restoring NP cells.Transcriptomic analyses were employed to identify the mediators influenced by mannose,with the thioredoxin-interacting protein(TXNIP)gene showing the most significant differences.Subsequently,small interfering RNA(siRNA)technology was used to demonstrate that TXNIP is the key gene through which mannose exerts its effects.Techniques such as colocalization analysis,molecular docking,and overexpression assays further confirmed the direct regulatory relationship between mannose and TXNIP.To elucidate the mechanism of action of mannose,metabolomics techniques were employed to pinpoint glutamine as a core metabolite affected by mannose.Next,various methods,including integrated omics data and the Gene Expression Omnibus(GEO)database,were used to validate the one-way pathway through which TXNIP regulates glutamine.Finally,the therapeutic effect of mannose on IVDD was validated,elucidating the mechanistic role of TXNIP in glutamine metabolism in both intradiscal and orally treated rats.Results:In both in vivo and in vitro experiments,it was discovered that mannose has potent efficacy in alleviating IVDD by inhibiting catabolism.From a mechanistic standpoint,it was shown that mannose exerts its anti-catabolic effects by directly targeting the transcription factor max-like protein X-interacting protein(MondoA),resulting in the upregulation of TXNIP.This upregulation,in turn,inhibits glutamine metabolism,ultimately accomplishing its anticatabolic effects by suppressing the mitogen-activated protein kinase(MAPK)pathway.More importantly,in vivo experiments have further demonstrated that compared with intradiscal injections,oral administration of mannose at safe concentrations can achieve effective therapeutic outcomes.Conclusions:In summary,through integrated multiomics analysis,including both in vivo and in vitro experiments,this study demonstrated that mannose primarily exerts its anti-catabolic effects on IVDD through the TXNIP-glutamine axis.These findings provide strong evidence supporting the potential of the use of mannose in clinical applications for alleviating IVDD.Compared to existing clinically invasive or pain-relieving therapies for IVDD,the oral administration of mannose has characteristics that are more advantageous for clinical IVDD treatment. 展开更多
关键词 D-MANNOSE intervertebral disc degeneration(IVDD) Thioredoxin-interacting protein(TXNIP) GLUTAMINE
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Role of macrophage in intervertebral disc degeneration
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作者 Yiming Dou Yiming Zhang +4 位作者 Yang Liu Xun Sun Xinyu Liu Bin Li Qiang Yang 《Bone Research》 2025年第1期15-34,共20页
Intervertebral disc degeneration is a degenerative disease where inflammation and immune responses play significant roles.Macrophages,as key immune cells,critically regulate inflammation through polarization into diff... Intervertebral disc degeneration is a degenerative disease where inflammation and immune responses play significant roles.Macrophages,as key immune cells,critically regulate inflammation through polarization into different phenotypes.In recent years,the role of macrophages in inflammation-related degenerative diseases,such as intervertebral disc degeneration,has been increasingly recognized.Macrophages construct the inflammatory microenvironment of the intervertebral disc and are involved in regulating intervertebral disc cell activities,extracellular matrix metabolism,intervertebral disc vascularization,and innervation,profoundly influencing the progression of disc degeneration.To gain a deeper understanding of the inflammatory microenvironment of intervertebral disc degeneration,this review will summarize the role of macrophages in the pathological process of intervertebral disc degeneration,analyze the regulatory mechanisms involving macrophages,and review therapeutic strategies targeting macrophage modulation for the treatment of intervertebral disc degeneration.These insights will be valuable for the treatment and research directions of intervertebral disc degeneration. 展开更多
关键词 DEGENERATION intervertebral INFLAMMATION
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Lumbar instability remodels cartilage endplate to induce intervertebral disc degeneration by recruiting osteoclasts via Hippo-CCL3 signaling 被引量:4
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作者 Hanwen Li Yingchuang Tang +7 位作者 Zixiang Liu Kangwu Chen Kai Zhang Sihan Hu Chun Pan Huilin Yang Bin Li Hao Chen 《Bone Research》 SCIE CAS CSCD 2024年第3期555-570,共16页
Degenerated endplate appears with cheese-like morphology and sensory innervation,contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population.1 However,the origin and... Degenerated endplate appears with cheese-like morphology and sensory innervation,contributing to low back pain and subsequently inducing intervertebral disc degeneration in the aged population.1 However,the origin and development mechanism of the cheese-like morphology remain unclear.Here in this study,we report lumbar instability induced cartilage endplate remodeling is responsible for this pathological change. 展开更多
关键词 DEGENERATION CARTILAGE intervertebral
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Extracellular vesicles loaded dual-network bioactive sealant via immunoregulation and annulus fibrosus repair for intervertebral disc herniation 被引量:1
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作者 Zetao Wang Haofei Li +5 位作者 Huitong Luo Hao Wang Zemin Ling Dafu Chen Qi Feng Xiaodong Cao 《Journal of Materials Science & Technology》 SCIE EI CAS CSCD 2024年第17期75-87,共13页
Intervertebral disc herniation(IVDH)is a common manifestation of intervertebral disc degeneration(IVDD)characterized by inflammation that results in the rupture of the annulus fibrosus(AF)and her-niation of the nucleu... Intervertebral disc herniation(IVDH)is a common manifestation of intervertebral disc degeneration(IVDD)characterized by inflammation that results in the rupture of the annulus fibrosus(AF)and her-niation of the nucleus pulposus(NP).While current clinical research primarily focuses on regulating the degenerative NP,the crucial role of the AF in maintaining the mechanical stability and metabolic balance of the intervertebral disc(IVD)has been overlooked.Resolving immunoregulation and AF repair is im-perative to effectively prevent recurrent herniation.Therefore,this study introduces a bioactive sealant(OD/GM/QCS-sEVs),which combines gelatin methacryloyl(GM)and oxidized dextran(OD)with quater-nized chitosan(QCS)and incorporates small extracellular vesicles(sEVs).The developed sealant possesses injectability,self-healing capabilities,tissue adhesiveness,and mechanical stability,with an average ad-hesive strength of 109.63 kPa.In vitro experiments demonstrate that OD/GM/QCS-sEVs effectively seal AF defects while preserving mechanical properties comparable to those of a normal IVD.Additionally,the sealant releases sEVs through a pH-responsive mechanism,thereby modulating macrophage polarization to the M2 phenotype via the NF-κB signaling pathway.This mechanism facilitates immunoregulation and anti-inflammatory effects,and promotes stem cell differentiation into fibrocartilage.Animal experiments confirm the ability of OD/GM/QCS-sEVs to seal defects,prevent proteoglycan loss,inhibit IVDD develop-ment,and promote AF regeneration.Overall,OD/GM/QCS-sEVs hold promise as an innovative bioactive sealant for recurrent herniation by resolving immunoregulation and AF regeneration. 展开更多
关键词 intervertebral disc herniation Extracellular vesicles Double-network hydrogel SEALANT IMMUNOREGULATION
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A new perspective on intervertebral disc calcification—from bench to bedside 被引量:1
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作者 Emanuel J.Novais Rajkishen Narayanan +5 位作者 Jose A.Canseco Koen van de Wetering Christopher K.Kepler Alan S.Hilibrand Alexander R.Vaccaro Makarand V.Risbud 《Bone Research》 SCIE CAS CSCD 2024年第1期50-61,共12页
Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniati... Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies. 展开更多
关键词 DEGENERATION metabolism intervertebral
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Understanding the Recovery of the Intervertebral Disc:A Comprehensive Review of In Vivo and In Vitro Studies
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作者 Faten Feki Fahmi Zaïri +4 位作者 Abderrahman Tamoud Melissa Moulart Rym Taktak Nader Haddar Fahed Zaïri 《Journal of Bionic Engineering》 SCIE EI CSCD 2024年第4期1919-1948,共30页
Within the consistent daily rhythm of human life,intervertebral discs endure a variety of complex loads beyond the influences of gravity and muscle forces,leading to significant morphological changes(in terms of volum... Within the consistent daily rhythm of human life,intervertebral discs endure a variety of complex loads beyond the influences of gravity and muscle forces,leading to significant morphological changes(in terms of volume,area,and height)as well as biomechanical alterations,including an increase in disc stiffness and a decrease in intradiscal pressure.Remarkably,the discs demonstrate an ability to regain their original morphological and biomechanical characteristics after a period of nocturnal rest.The preservation of normal disc function is critically dependent on this recovery phase,which serves to forestall premature disc degeneration.This phenomenon of disc recovery has been extensively documented through numerous in vivo studies employing advanced clinical techniques such as Magnetic Resonance Imaging(MRI),stadiometry,and intradiscal pressure measurement.However,the findings from in vitro studies present a more complex picture,with reports varying between full recovery and only partial recuperation of the disc properties.Moreover,research focusing on degenerated discs in vitro has shed light on the quantifiable impact of degeneration on the disc ability to recover.Fluid dynamics within the disc are considered a primary factor in recovery,yet the disc intricate multiscale structure and its viscoelastic properties also play key roles.These elements interact in complex ways to influence the recovery mechanism,particularly in relation to the overall health of the disc.The objective of this review is to collate,analyze,and critically evaluate the existing body of in vivo and in vitro research on this topic,providing a comprehensive understanding of disc recovery processes.Such understanding offers a blueprint for future advancements in medical treatments and bionic engineering solutions designed to mimic,support,and enhance the natural recovery processes of intervertebral discs. 展开更多
关键词 intervertebral disc RECOVERY In vivo vs.in vitro studies DEGENERATION Viscoelastic effects Fluid dynamics
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Therapy of auricular subcutaneous penetration needling combined with row acupuncture at the meridian sinew in 103 cases of prolapse of lumbar intervertebral disc
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作者 侯献兵 刘英莉 +3 位作者 王利春 卢威威 宋书昌 贾春生 《World Journal of Acupuncture-Moxibustion》 CSCD 2015年第2期63-66,共4页
Objective To observe the clinical efficacy of auricular subcutaneous penetration needling combining with row acupuncture at meridian sinew on prolapse of lumbar intervertebral disc. Methods One hundred and three patie... Objective To observe the clinical efficacy of auricular subcutaneous penetration needling combining with row acupuncture at meridian sinew on prolapse of lumbar intervertebral disc. Methods One hundred and three patients with prolapse of lumbar intervertebral disc were treated with a combined treatment of auricular subcutaneous penetration needling and row acupuncture at meridian sinew. Results Of 103 patients, 46 cases were cured, 33 were markedly effective, 21 effective and 3 ineffective. The total effective rate was 97.1% (100/103). Conclusion The combined treatment of auricular subcutaneous penetration needling and row acupuncture at meridian sinew has a significant efficacy for the treatment of prolapse of lumbar intervertebral disc. 展开更多
关键词 prolapse of lumbar intervertebral disc auricular subcutaneouspenetration needling row acupuncture at meridian sinew
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EFFECT OF ACUPUNCTURE ON POST-OPERATIVE FUNCTIONAL RECOV-ERY IN PATIENTS WITH LUMBAR INTERVERTEBRAL DISC PROTRUSION
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作者 赵斌修 王坤正 +3 位作者 赵杰修 黄向辉 王建中 柏传毅 《World Journal of Acupuncture-Moxibustion》 2008年第1期22-28,共7页
Objective To observe the influence of acupuncture on the post-operative rehabilitation in patients undergoing vertebral pulp extraction due to lumbar intervertebral disc protrusion (LIDP) so as to evaluate its effic... Objective To observe the influence of acupuncture on the post-operative rehabilitation in patients undergoing vertebral pulp extraction due to lumbar intervertebral disc protrusion (LIDP) so as to evaluate its efficacy in the treatment of lumbago induced by LIDP. Methods A total of 69 patients undergoing vertebral pulp extraction were randomized into acupuncture group ( n = 35) and control group ( n = 34). Patients of acupuncture group were treated with routine rehabilitation method and electroacupuncture (EA) stimulation on Zhìbiān (秩边 BL54) and Wěizhōng (委中 BL40), acupuncture on Shènshū ( 肾俞 BL23), Dàchángshū (大肠俞 BL25), BL54, BL40, Jiájǐ (夹脊 EX-B 2), Shàngliáo (上髎 BL31), etc., and cupping on BL40, with 15 days being a therapeutic course and for average 7. 36 courses. Patients of control group were treated with simple rehabilitation method. Functional recovery state was judged before and after surgery by using the standards of Japanese Orthopedic Association (JOA). Results The average recovery rates of 3 months, 6 months and one year after surgery were 49.93% ,90.31% and 95.08% separately in acupuncture group, and 26.24% ,63.42% and 71.36% successively in control group. The recovery rates of acupuncture group were significantly higher than those of control group at the same time-points (P〈0. 05). Conclusion Acupuncture has a definite effect on promoting post-operative functional recovery in LIDP patients undergoing vertebral pulp extraction and spinal fusion. 展开更多
关键词 Lumbar intervertebral disc protrusion Acupuncture Rehabilitation treatment
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Applied anatomy of intrusive operations of lumbar intervertebral foramen 被引量:2
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作者 You-liang WEN Si-guo YUAN +1 位作者 Yi-kai LI Yu-cong ZOU 《赣南医学院学报》 2015年第2期165-172,共8页
Objective:To provide anatomical datum for intrusive operations of lumbar intervertebral foramen,especially that using acupuncture-knife as intrusive tool.Methods:To dissect 10 antisepsis cadavers and observe the expos... Objective:To provide anatomical datum for intrusive operations of lumbar intervertebral foramen,especially that using acupuncture-knife as intrusive tool.Methods:To dissect 10 antisepsis cadavers and observe the exposed blood vessels,ligaments,nerves and their adjacent relations in L1/2~L5/S1intervertebral foramen.Results:Lumbar intervertebral foramen exit zones were almost sealed by nerves and blood vessels.There were two zones with relatively no blood vessel and nerve(triangular working zones)located in the midpoint of the distance between two adjacent roots of transverse processus,and clung to lamina of vertebral arch,and they were also found upon the margo superior of the root of transverse processus,but the ascending lumbar vein or(and)the rami anastomoticus between the remi inferior of intervertebral vein and lumbar veins were observed in 12%triangular working zones upon the margo superior of root of transverse processus.Conclusions:"Triangular working zone"was relatively avascular zone.Pay attention to the possibilty of presence of blood vessels on the entrance passage of intrusive operations on lumbar side rear.The needlepoint should be pierced at the midpoint of the distance between two adjacent roots of transverse processus and cling to the outer edge of lamina of vertebral arch when doing the foraminal lumbar puncture.As lumbar intervertebral foramina exit zone was almost sealed by nerves and blood vessels,blind incising and debonding with acupuncture-knife in this area was relatively much more dangerous. 展开更多
关键词 intervertebral foramen Injection through intervertebral foramen Acupotomy / Acupuncture-knife Triangular working zone Lumbar disc herniation
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Observation of efficacy on prolapse of lumbar intervertebral disc treated with body acupuncture and wrist-ankle acupuncture 被引量:6
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作者 何常春 周露 +1 位作者 欧阳世杰 李明 《World Journal of Acupuncture-Moxibustion》 2009年第3期31-36,共6页
Objective To observe the clinical effects of body acupuncture and wrist-ankle acupuncture on prolapse of lumbar intervertebral disc, Methods One hundred and eighty cases of prolapse of lumbar intervertebral disc were ... Objective To observe the clinical effects of body acupuncture and wrist-ankle acupuncture on prolapse of lumbar intervertebral disc, Methods One hundred and eighty cases of prolapse of lumbar intervertebral disc were randomly divided into body acupuncture and wrist-ankle acupuncture group (observation group) and simple body acupuncture group (control group), 90 cases in each one. In observation group, body acupuncture was applied on Ahshi points of lumbar region, lumbar Jiájǐ (夹脊EX-B 2), Dàchángshú(大肠俞 BL 25), etc. and wrist-ankle acupuncture was applied on lower No. 4, 5 and 6 regions. In control group, simple body acupuncture was applied on the same points as observation group. Results The lumbar vertebral function and pain scale were improved in either group in comparison before and after treatment (P〈0.05). Concerning pain improvement, the total effective rate was 95.6% in observation group, which was superior to that (86.7%) in control group (P〈0.05). Concerning the improvement of lumbar vertebral function, the total effective rate was 90.0% in observation group and 93.3% in control group, without significant difference between two groups (P〉0.05). Conclusion Combined therapy of body acupuncture and wrist-ankle acupuncture demonstrates apparent analgesia in prolapse of lumbar intervertebral disc. 展开更多
关键词 Prolapse of Lumbar intervertebral Disc Acupuncture Therapy Wrist-Ankle Acupunc-ture Body Acupuncture
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