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1.
Zhonghua Yi Xue Za Zhi ; 104(27): 2502-2512, 2024 Jul 16.
Artigo em Chinês | MEDLINE | ID: mdl-38978374

RESUMO

Cervical artificial disc replacement preserves the range of motion after the decompression, and this technology has achieved good clinical results. The indications, surgical procedures, and perioperative management of cervical disc arthroplasty are different from traditional anterior cervical decompression and fusion. The Health Management and Enhanced Recovery of Cervical Spine Disorders Committee, Chinese Research Hospital Association has established an expert group to draw up this expert consensus through literature analysis and professional discussions. The purpose of this consensus is to standardize the surgical indications and patient selection of cervical artificial disc replacement, to guide surgical procedures and perioperative management, and to improve the clinical outcomes of cervical artificial disc replacement.


Assuntos
Vértebras Cervicais , Substituição Total de Disco , Humanos , Substituição Total de Disco/métodos , Vértebras Cervicais/cirurgia , Fusão Vertebral/métodos , Disco Intervertebral/cirurgia , Descompressão Cirúrgica/métodos , Consenso , Amplitude de Movimento Articular
2.
PeerJ ; 12: e17464, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006038

RESUMO

Objective: The mechanisms of intervertebral disc degeneration (IVDD) in low back pain (LBP) patients are multiples. In this study, we attempt to investigate whether melatonergic system plays a potential role in IVDD patients with LBP by analyzing their clinical specimens. The fucus will be given to the correlation between the melatonin receptor expression and intervertebral disc tissue apoptosis. Methods: In this clinical study, 107 lumbar intervertebral disc nucleus pulposus (NP) specimens from patients with LBP were collected with patients' consents. The disc height (DH) discrepancy ratio, range of motion and sagittal parameters of the pathological plane were measured and Pfirrmann grade was used to classified the grades of IVDD level. Discs at grades 1-3 were served as normal control and grades 4-5 were considered as IVDD. The expression levels of melatonin receptor 1A (MT1) and 1B (MT2) were measured by immunohistochemistry. The apoptosis of NP was assessed using TUNEL staining. Their potential associations among MT1/2, DH, apoptosis, sagittal parameters with IVDD and LBP were evaluated with statistical analysis. Results: The incidence of IVDD was positively associated with age and negatively related to VAS scores for LBP (p < 0.001). Patients with higher degree of IVDD also have higher DH discrepancy ratio (p < 0.001), higher prevalence of lumbar instability (p = 0.003) and higher cell apoptosis compared to the control. Nevertheless, no statistically significant correlation was identified between Pfirrmann grade and lumbar sagittal parameters. MT1 and MT2 both were highly expressed in the NP tissues. Importantly, MT1 expression but not MT2 was significantly increased in the intervertebral disc tissue of patients with IVDD and its level correlated well with cell apoptosis level and the severity of IVDD as well as lower VAS scores for LBP. Conclusion: The highly elevated MT1 expression was found in NP tissues of patients with IVDD and LBP compared to the control. This phenomenon probably reflects the compensating response of the body to the pathological alteration of the IVDD and LBP. Therefore, these findings provide the novel information to use selective agonists of MT1 to target IVDD and LBP clinically.


Assuntos
Apoptose , Degeneração do Disco Intervertebral , Dor Lombar , Humanos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Dor Lombar/patologia , Dor Lombar/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Vértebras Lombares/patologia , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Idoso , Disco Intervertebral/patologia , Disco Intervertebral/metabolismo
3.
Med Sci Monit ; 30: e944645, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39014873

RESUMO

BACKGROUND Lower back pain is a common problem in the general population. Medical treatment is the first choice for patients without severe pain and major motor weakness. If patients do not benefit from conservative treatment, minimally invasive treatment is recommended. Ozone nucleolysis has recently been used to reduce pain and inflammation in herniated discs and other spinal conditions. This retrospective study from a single center aimed to evaluate the effects of ozone disc nucleolysis in the management of 149 patients with herniated lumbar intervertebral discs from 2022 to 2024. MATERIAL AND METHODS Between 2022 and 2024, intradiscal ozone nucleolysis was performed under operating room C-arm scopy in 149 patients who received medical treatment and physical therapy without surgical indication but did not benefit, and the results were evaluated retrospectively. Visual Analog Scale (VAS) scores and Oswestry Disability Index (ODI) scores were recorded before the procedure, and at 1 month, 3 months, 6 months, and 1 year. RESULTS The study enrolled 149 patients, comprising 61 males and 88 females, with an overall mean age of 43.9±4.7 years. The procedure was performed as 1 level in 138 patients and 2 levels in 11 patients. Among patients who underwent procedures based on lumbar MRI findings, 15 involved the L3-L4 intervertebral disc, 3 involved both the L3-L4 and L4-L5 discs, 90 involved the L4-L5 disc, and 31 involved the L5-S1 disc. Post-procedure VAS scores were significantly different at 1 month and 6 months (P<0.05). Post-procedure ODI scores were also significantly different at 1 month and 6 months. CONCLUSIONS Due to its low complication rate and effectiveness in treating lumbar disc herniation, ozone chemonucleolysis should be considered for use in patients who do not have a surgical indication or do not accept surgical intervention and did not benefit from medical treatment and physical therapy.


Assuntos
Deslocamento do Disco Intervertebral , Vértebras Lombares , Ozônio , Humanos , Masculino , Feminino , Ozônio/uso terapêutico , Ozônio/farmacologia , Adulto , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Pessoa de Meia-Idade , Dor Lombar/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Resultado do Tratamento , Medição da Dor , Disco Intervertebral/cirurgia
4.
Turk Neurosurg ; 34(4): 640-646, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38874242

RESUMO

AIM: To explore the relationship between the retroperitoneal vasculature and anterior surface of the lower spine, and to establish values for aiding in prediction of the pertinence of anterior approach at the L4-L5 and L5-S1 intervertebral discs. MATERIAL AND METHODS: The study included 13 fresh human cadavers. After exploration of the abdominal cavity and removal of the visceral organs, the vasculature, and anterior spinal surface were revealed beneath the lower extension of the perirenal fascia. Morphometric measurements of the great vessels and the intervertebral discs were obtained. All measurements were analyzed and presented as mean and standard deviation. Differences in the values between sexes were assessed. RESULTS: The anterior height of the L4-L5 and L5-S1 intervertebral disc was 6.8 ± 0.81 mm and 6.7 ± 0.99 mm, respectively. The widths of the aorta, inferior vena cava, right and left common iliac arteries, and right, and left common iliac veins were 16.4 ± 3.58, 20.6 ± 3.36, 11.5 ± 2.32, 11.5 ± 2.43, 14.7 ± 3.13, and 15.5 ± 3.27 mm, respectively. The mean aortic bifurcation angle was 45.5°. The aortic bifurcation was located above the lower endplate of the L4 vertebrae in 53.8% of the cadavers. The area of the interarterial and interiliac trigones was 14.6 ± 5.33 cm < sup > 2 < /sup > and 7.1 ± 4.35 cm2, respectively. No statistically significant differences were noted between the sexes. CONCLUSION: An elaborate radiological examination of the vasculature should be performed prior to surgery to avoid unwanted vascular complications during the anterior approach. Knowing the area of the interarterial and interiliac triangles and the aortic bifurcation location could be aid in assessing the safe working zone.


Assuntos
Cadáver , Disco Intervertebral , Vértebras Lombares , Humanos , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/cirurgia , Masculino , Feminino , Disco Intervertebral/anatomia & histologia , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/cirurgia , Pessoa de Meia-Idade , Idoso , Veia Ilíaca/anatomia & histologia , Artéria Ilíaca/anatomia & histologia , Artéria Ilíaca/diagnóstico por imagem , Veia Cava Inferior/anatomia & histologia , Veia Cava Inferior/cirurgia , Espaço Retroperitoneal/anatomia & histologia , Adulto
5.
J Biomech ; 171: 112159, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38852480

RESUMO

Degenerative disc disease (DDD), regardless of its phenotype and clinical grade, is widely associated with low back pain (LBP), which remains the single leading cause of disability worldwide. This work provides a quantitative methodology for comparatively investigating artificial IVD degeneration via two popular approaches: enzymatic denaturation and fatigue loading. An in-vitro animal study was used to study the time-dependent responses of forty fresh juvenile porcine thoracic IVDs in conjunction with inverse and forward finite element (FE) simulations. The IVDs were dissected from 6-month-old-juvenile pigs and equally assigned to 5 groups (intact, denatured, low-level, medium-level, high-level fatigue loading). Upon preloading, a sinusoid cyclic load (Peak-to-peak/0.1-to-0.8 MPa) was applied (0.01-10 Hz), and dynamic-mechanical-analyses (DMA) was performed. The DMA outcomes were integrated with a robust meta-model analysis to quantify the poroelastic IVD characteristics, while specimen-specific FE models were developed to study the detailed responses. The results demonstrated that enzymatic denaturation had a more significantly pronounced effect on the resistive strength and shock attenuation capabilities of the intervertebral discs. This can be attributed to the simultaneous disruption of the collagen fibers and water-proteoglycan bonds induced by trypsin digestion. Fatigue loading, on the other hand, primarily influenced the disc's resistance to deformation in a frequency-dependent pattern, where alterations were most noticeable at low loading frequencies. This study confirms the intricate interplay between the biochemical changes induced by enzymatic processes and the mechanical behavior stemming from fatigue loading, suggesting the need for a comprehensive approach to closely mimic the interrelated multifaceted processes of human disc degeneration.


Assuntos
Análise de Elementos Finitos , Degeneração do Disco Intervertebral , Disco Intervertebral , Animais , Degeneração do Disco Intervertebral/fisiopatologia , Disco Intervertebral/fisiopatologia , Suínos , Estresse Mecânico , Suporte de Carga/fisiologia , Desnaturação Proteica , Fenômenos Biomecânicos , Modelos Biológicos
6.
Med Eng Phys ; 129: 104189, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38906572

RESUMO

Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.


Assuntos
Sobrevivência Celular , Força Compressiva , Análise de Elementos Finitos , Glucose , Disco Intervertebral , Resistência à Tração , Glucose/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/citologia , Modelos Biológicos , Fenômenos Biomecânicos , Estresse Mecânico
7.
Front Biosci (Landmark Ed) ; 29(6): 224, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38940022

RESUMO

BACKGROUND: The objective of this research was to identify differentially expressed genes (DEGs) related to ferroptosis in the annulus fibrosus (AF) during intervertebral disc degeneration (IDD). METHODS: We analyzed gene data from degenerated and normal AF obtained from the GSE70362 and GSE147383 datasets. An analysis to determine the functional significance of the DEGs was conducted, followed by the creation of a network illustrating the interactions between proteins. We further analyzed the immune infiltration of the DEGs and determined the hub DEGs using LASSO regression analysis. Finally, we identified the hub ferroptosis-related DEGs (FRDEGs) and verified their expression levels using Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot, Immunohistochemical Staining (IHC), and Immunofluorescence (IF). RESULTS: By analyzing the GSE70362 and GSE147383 datasets, we identified 118 DEGs. In degenerative AF groups, we observed a significant increase in immune infiltration of resting memory CD4+ T cells. LASSO regression analysis revealed 9 hub DEGs. The construction of a Receiver Operating Characteristic (ROC) curve yielded an Area Under the Curve (AUC) value of 0.762. Furthermore, we found that MGST1 is a hub gene related to ferroptosis. Our examination of immune infiltration indicated that MGST1 primarily influences macrophage M0 in different immune cell expression groups. Finally, our observations revealed a marked upregulation of MGST1 expression in the degenerated annulus fibrosus tissue. CONCLUSION: Our findings indicate an upsurge in MGST1 levels within degenerative AF, potentially playing a crucial role in the exacerbation of IDD. These findings provide a foundation for further exploration of the pathological mechanisms underlying IDD and offer potential drug targets for intervention.


Assuntos
Anel Fibroso , Biologia Computacional , Ferroptose , Glutationa Transferase , Degeneração do Disco Intervertebral , Humanos , Anel Fibroso/metabolismo , Anel Fibroso/patologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Ferroptose/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Mapas de Interação de Proteínas/genética , Glutationa Transferase/genética , Glutationa Transferase/metabolismo
8.
Cell Rep ; 43(6): 114342, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38865240

RESUMO

The nucleus pulposus (NP) in the intervertebral disc (IVD) arises from embryonic notochord. Loss of notochordal-like cells in humans correlates with onset of IVD degeneration, suggesting that they are critical for healthy NP homeostasis and function. Comparative transcriptomic analyses identified expression of progenitor-associated genes (GREM1, KRT18, and TAGLN) in the young mouse and non-degenerated human NP, with TAGLN expression reducing with aging. Lineage tracing using Tagln-CreERt2 mice identified peripherally located proliferative NP (PeriNP) cells in developing and postnatal NP that provide a continuous supply of cells to the entire NP. PeriNP cells were diminished in aged mice and absent in puncture-induced degenerated discs. Single-cell transcriptomes of postnatal Tagln-CreERt2 IVD cells indicate enrichment for TGF-ß signaling in Tagln descendant NP sub-populations. Notochord-specific removal of TGF-ß/BMP mediator Smad4 results in loss of Tagln+ cells and abnormal NP morphologies. We propose Tagln+ PeriNP cells are potential progenitors crucial for NP homeostasis.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Células-Tronco , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/genética , Animais , Humanos , Camundongos , Células-Tronco/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Fator de Crescimento Transformador beta/metabolismo
9.
Sci Rep ; 14(1): 13181, 2024 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849364

RESUMO

The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1-S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.


Assuntos
Análise de Elementos Finitos , Amplitude de Movimento Articular , Escoliose , Fusão Vertebral , Humanos , Escoliose/cirurgia , Escoliose/fisiopatologia , Adulto , Masculino , Fenômenos Biomecânicos , Fusão Vertebral/métodos , Parafusos Pediculares , Tomografia Computadorizada por Raios X , Estresse Mecânico , Disco Intervertebral/cirurgia , Disco Intervertebral/fisiopatologia , Disco Intervertebral/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Vértebras Torácicas/fisiopatologia
10.
Cells ; 13(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38891119

RESUMO

Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.


Assuntos
Alginatos , Modelos Animais de Doenças , Degeneração do Disco Intervertebral , Disco Intervertebral , Animais , Cães , Alginatos/química , Alginatos/farmacologia , Disco Intervertebral/cirurgia , Disco Intervertebral/patologia , Disco Intervertebral/efeitos dos fármacos , Coelhos , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/terapia , Estudo de Prova de Conceito , Géis , Células da Medula Óssea/citologia , Células-Tronco Mesenquimais/citologia , Imageamento por Ressonância Magnética , Masculino , Transplante de Medula Óssea/métodos
11.
Sci Adv ; 10(23): eadj3194, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848366

RESUMO

Persistent inflammation has been associated with severe disc degeneration (DD). This study investigated the effect of prolonged nuclear factor κB (NF-κB) activation in DD. Using an inducible mouse model, we genetically targeted cells expressing aggrecan, a primary component of the disc extra cellular matrix, for activation of the canonical NF-κB pathway. Prolonged NF-κB activation led to severe structural degeneration accompanied by increases in gene expression of inflammatory molecules (Il1b, Cox2, Il6, and Nos2), chemokines (Mcp1 and Mif), and catabolic enzymes (Mmp3, Mmp9, and Adamts4). Increased recruitment of proinflammatory (F4/80+,CD38+) and inflammatory resolving (F4/80+,CD206+) macrophages was observed within caudal discs. We found that the secretome of inflamed caudal disc cells increased macrophage migration and inflammatory activation. Lumbar discs did not exhibit phenotypic changes, suggestive of regional spinal differences in response to inflammatory genetic overactivation. Results suggest prolonged NF-κB activation can induce severe DD through increases in inflammatory cytokines, chemotactic proteins, catabolic enzymes, and the recruitment and activation of macrophage cell populations.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Macrófagos , NF-kappa B , Animais , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , NF-kappa B/metabolismo , Macrófagos/metabolismo , Camundongos , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação/patologia , Citocinas/metabolismo , Transdução de Sinais
12.
Med Eng Phys ; 127: 104158, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38692761

RESUMO

BACKGROUND: The intervertebral disc exhibits not only strain rate dependence (viscoelasticity), but also significant asymmetry under tensile and compressive loads, which is of great significance for understanding the mechanism of lumbar disc injury under physiological loads. OBJECTIVE: In this study, the strain rate sensitive and tension-compression asymmetry of the intervertebral disc were analyzed by experiments and constitutive equation. METHOD: The Sheep intervertebral disc samples were divided into three groups, in order to test the strain rate sensitive mechanical behavior, and the internal displacement as well as pressure distribution. RESULTS: The tensile stiffness is one order of magnitude smaller than the compression stiffness, and the logarithm of the elastic modulus is approximately linear with the logarithm of the strain rate, showing obvious tension-compression asymmetry and rate-related characteristics. In addition, the sensitivity to the strain rate is the same under these two loading conditions. The stress-strain curves of unloading and loading usually do not coincide, and form a Mullins effect hysteresis loop. The radial displacement distribution is opposite between the anterior and posterior region, which is consistent with the stress distribution. By introducing the damage factor into ZWT constitutive equation, the rate-dependent viscoelastic and weakening behavior of the intervertebral disc can be well described.


Assuntos
Força Compressiva , Disco Intervertebral , Estresse Mecânico , Animais , Disco Intervertebral/fisiologia , Ovinos , Fenômenos Biomecânicos , Resistência à Tração , Suporte de Carga , Elasticidade
13.
Ageing Res Rev ; 98: 102323, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38734147

RESUMO

Oxidative stress is one of the main driving mechanisms of intervertebral disc degeneration(IDD). Oxidative stress has been associated with inflammation in the intervertebral disc, cellular senescence, autophagy, and epigenetics of intervertebral disc cells. It and the above pathological mechanisms are closely linked through the common hub reactive oxygen species(ROS), and promote each other in the process of disc degeneration and promote the development of the disease. This reveals the important role of oxidative stress in the process of IDD, and the importance and great potential of IDD therapy targeting oxidative stress. The efficacy of traditional therapy is unstable or cannot be maintained. In recent years, due to the rise of materials science, many bioactive functional materials have been applied in the treatment of IDD, and through the combination with traditional drugs, satisfactory efficacy has been achieved. At present, the research review of antioxidant bioactive materials in the treatment of IDD is not complete. Based on the existing studies, the mechanism of oxidative stress in IDD and the common antioxidant therapy were summarized in this paper, and the strategies based on emerging bioactive materials were reviewed.


Assuntos
Antioxidantes , Degeneração do Disco Intervertebral , Estresse Oxidativo , Estresse Oxidativo/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Humanos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/terapia , Degeneração do Disco Intervertebral/tratamento farmacológico , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/efeitos dos fármacos
14.
Matrix Biol ; 131: 46-61, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38806135

RESUMO

Syndecan 4 (SDC4), a cell surface heparan sulfate proteoglycan, is known to regulate matrix catabolism by nucleus pulposus cells in an inflammatory milieu. However, the role of SDC4 in the aging spine has never been explored. Here we analyzed the spinal phenotype of Sdc4 global knockout (KO) mice as a function of age. Micro-computed tomography showed that Sdc4 deletion severely reduced vertebral trabecular and cortical bone mass, and biomechanical properties of vertebrae were significantly altered in Sdc4 KO mice. These changes in vertebral bone were likely due to elevated osteoclastic activity. The histological assessment showed subtle phenotypic changes in the intervertebral disc. Imaging-Fourier transform-infrared analyses showed a reduced relative ratio of mature collagen crosslinks in young adult nucleus pulposus (NP) and annulus fibrosus (AF) of KO compared to wildtype discs. Additionally, relative chondroitin sulfate levels increased in the NP compartment of the KO mice. Transcriptomic analysis of NP tissue using CompBio, an AI-based tool showed biological themes associated with prominent dysregulation of heparan sulfate GAG degradation, mitochondria metabolism, autophagy, endoplasmic reticulum (ER)-associated misfolded protein processes and ER to Golgi protein processing. Overall, this study highlights the important role of SDC4 in fine-tuning vertebral bone homeostasis and extracellular matrix homeostasis in the mouse intervertebral disc.


Assuntos
Envelhecimento , Doenças Ósseas Metabólicas , Homeostase , Camundongos Knockout , Sindecana-4 , Animais , Camundongos , Sindecana-4/metabolismo , Sindecana-4/genética , Envelhecimento/metabolismo , Envelhecimento/genética , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Doenças Ósseas Metabólicas/patologia , Microtomografia por Raio-X , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Matriz Extracelular/metabolismo , Matriz Extracelular/genética , Coluna Vertebral/metabolismo , Coluna Vertebral/patologia , Coluna Vertebral/diagnóstico por imagem , Anel Fibroso/metabolismo , Anel Fibroso/patologia , Osteoclastos/metabolismo
15.
Eur Spine J ; 33(6): 2439-2450, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38705903

RESUMO

PURPOSE: To describe the physiology of spinal growth in patients with adolescent idiopathic scoliosis (AIS). METHODS: Narrative review of the literature with a focus on mechanisms of growth. RESULTS: In his landmark publication On Growth and Form, D'Arcy Thompson wrote that the anatomy of an organism reflects the forces it is subjected to. This means that mechanical forces underlie the shape of tissues, organs and organisms, whether healthy or diseased. AIS is called idiopathic because the underlying cause of the deformation is unknown, although many factors are  associated. Eventually, however, any deformity is due to mechanical forces. It has long been shown that the typical curvature and rotation of the scoliotic spine could result from vertebrae and intervertebral discs growing faster than the ligaments attached to them. This raises the question why in AIS the ligaments do not keep up with the speed of spinal growth. The spine of an AIS patient deviates from healthy spines in various ways. Growth is later but faster, resulting in higher vertebrae and intervertebral discs. Vertebral bone density is lower, which suggests  less spinal compression. This also preserves the notochordal cells and the swelling pressure in the nucleus pulposus. Less spinal compression is due to limited muscular activity, and low muscle mass indeed underlies the lower body mass index (BMI) in AIS patients. Thus, AIS spines grow faster because there is less spinal compression that counteracts the force of growth (Hueter-Volkmann Law). Ligaments consist of collagen fibres that grow by tension, fibrillar sliding and the remodelling of cross-links. Growth and remodelling are enhanced by dynamic loading and by hormones like estrogen. However, they are opposed by static loading. CONCLUSION: Increased spinal elongation and reduced ligamental growth result in differential strain and a vicious circle of scoliotic deformation. Recognising the physical and biological cues that contribute to differential growth  allows earlier diagnosis of AIS and prevention in children at risk.


Assuntos
Escoliose , Coluna Vertebral , Humanos , Escoliose/fisiopatologia , Adolescente , Fenômenos Biomecânicos/fisiologia , Disco Intervertebral/fisiopatologia
16.
Eur Spine J ; 33(6): 2405-2419, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38730057

RESUMO

PURPOSE: In vivo studies of continuous lumbar sagittal plane motion have found passive intervertebral motion to be more uneven in patients with chronic nonspecific low back pain (CNSLBP) than healthy controls, but the mechanisms are unclear. This study aimed to compare patients with CNSLBP with a matched group of pain-free controls for intervertebral restraint during passive recumbent bending. METHODS: Seventeen patients with CNSLBP and minimal disc degeneration who had quantitative fluoroscopy investigations were matched to 17 healthy controls from a database acquired using the same imaging protocol. The entire database (n = 136) was examined for clustering of peaking times, magnitudes and ROM of the first derivatives of the intervertebral angle/motion curves (PTFD, PMFD and ROM) during flexion and return that might introduce confounding. The groups were then compared for differences in these variables. RESULTS: There were significant segmental ROM differences among clusters in the database when PMFD and ROM were used as clustering variables, indicating heterogeneity. However, in the patient-control study, it was PTFD (velocity) that differentiated the groups. At L5-S1, this was at 10.82% of the motion path compared with 25.06% in the controls (p = 0.0002). For L4-5, PTFD was at 23.42% of the motion path in patients and 16.33% in controls (p = 0.0694) suggesting a reduced initial bending moment there. There were no significant differences for PMFD or ROM. CONCLUSION: Peaking time of passive intervertebral velocity occurs early at L5-S1 in patients with CNSLBP; however, these findings should be treated with caution pending their replication. Future studies should explore relationships with altered disc pressures and biochemistry. Usefulness for monitoring regenerative disc therapies should be considered.


Assuntos
Dor Lombar , Amplitude de Movimento Articular , Humanos , Dor Lombar/terapia , Dor Lombar/fisiopatologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Amplitude de Movimento Articular/fisiologia , Vértebras Lombares/diagnóstico por imagem , Disco Intervertebral/fisiopatologia , Disco Intervertebral/diagnóstico por imagem , Dor Crônica/terapia , Dor Crônica/fisiopatologia , Estudos de Casos e Controles , Estudos de Coortes
17.
World Neurosurg ; 188: e326-e333, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38796152

RESUMO

OBJECTIVE: This study analyzed and explored the relationship between isthmic spondylolisthesis and disc degeneration by comparing the degree of disc degeneration in patients with isthmic spondylolisthesis, lumbar disc herniation, and asymptomatic healthy individuals. METHODS: This study included a total of 138 cases, consisting of L5-S1 single segment lesion patients and a normal lumbar spine population. The cases were divided into 3 groups based on the type of disease: fifty eight cases in the isthmic spondylolisthesis (IS) group, 50 cases in the lumbar disc herniation (LDH) group, and 30 cases in the normal lumbar vertebrae (NLV) group. RESULTS: The research findings indicate that the proportion of intervertebral disc degeneration in the LDH group is significantly higher than that in the IS group and NLV group (65.3% vs. 33.3% vs. 25.8%, P < 0.05). The Pfirrmann grades of lumbar intervertebral discs (L1-L4) in the LDH group are significantly higher than those in the IS group and NLV group (P < 0.05), and the intervertebral height index (IHI) (L1-L4) of lumbar vertebrae in the LDH group is significantly lower than that in the IS group and NLV group (P < 0.05). CONCLUSIONS: The results showed that the degree of intervertebral disc degeneration in patients with isthmic spondylolisthesis was lighter than that in patients with LDH, and even similar to that in healthy individuals. The occurrence of IS may have slowed down the degeneration of nonaffected segment intervertebral discs through certain factors.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Vértebras Lombares , Espondilolistese , Humanos , Espondilolistese/diagnóstico por imagem , Masculino , Feminino , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Degeneração do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/patologia , Idoso
18.
Neurol Med Chir (Tokyo) ; 64(6): 222-229, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38719578

RESUMO

The detailed changes in disc properties after intradiscal injection of condoliase remain controversial. At 3 and 9 months after administration, radiographic changes in discs were investigated. A total of 41 patients (men, 25; median age, 46 years) who underwent regular follow-up magnetic resonance imaging at 3 and 9 months after administration without additional invasive therapy were retrospectively investigated. The intensity changes of the nucleus pulposus based on the Pfirrmann disc grading system, midsagittal disc height, and maximum protrusion length of herniation were assessed. In addition, disc height changes were compared between 24 patients aged <50 years (young group) and 17 patients aged ≥50 years (over 50s group). The overall mean disc heights were 9.1, 7.5, and 7.6 mm preoperatively, at 3 months, and at 9 months, respectively, with a significant reduction at 3 months (P < 0.001) and no significant changes thereafter. The mean maximum protrusion length of herniation significantly and gradually decreased. The overall proportions of Pfirrmann disc grades after administration were equivalent between 3 and 9 months. However, the recovery from Pfirrmann disc grades IV to III was confirmed in 8 of 17 cases (47.1%) between 3 and 9 months, whereas 6 of 20 cases (30.0%) showed a decline from III to IV. Patients in the young group with pretreatment disc height >11 mm had the greatest reduction in disc height than the over 50s group. In conclusion, the clinical outcomes in the over 50s group were comparable to those in the young group after injection of condoliase, whereas young patients with higher disc were more susceptible to disc height reduction.


Assuntos
Deslocamento do Disco Intervertebral , Vértebras Lombares , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Vértebras Lombares/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Disco Intervertebral/diagnóstico por imagem , Hialuronoglucosaminidase/administração & dosagem , Hialuronoglucosaminidase/uso terapêutico , Imageamento por Ressonância Magnética
19.
Clin Biomech (Bristol, Avon) ; 116: 106266, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821035

RESUMO

BACKGROUND: Most ball-in-socket artificial lumbar disc implanted in the spine result in increased hypermobility of the operative level and overloading of the facet joint. METHODS: A finite element model was established and validated for the lumbar spine (L1-L5). The structure of the Mobidisc prosthesis was modified, resulting in the development of two new intervertebral disc prostheses, Movcore and Mcopro. The prostheses were implanted into the L3/L4 level to simulate total disc replacement, and the biomechanical properties of the lumbar spine model were analyzed after the operation. FINDINGS: Following the implantation of the prostheses, the mobility of operative level, peak stress of lumbar spine models, and peak stress of facet joint increased. The performance of mobility was found to be more similar between Movcore and Mobidisc. The mobility and facet joint peak stress of the Mcopro model decreased progressively with an increase in the Young's modulus of the artificial annulus during flexion, extension, and lateral bending. Among all the models, the Mcopro50 model had the mobility closest to the intact model. It showed a 3% decrease in flexion, equal range of motion in extension, a 9% increase in left lateral bending, a 7% increase in right lateral bending, and a 3% decrease in axial rotation. INTERPRETATION: The feasibility of the new intervertebral disc prostheses, Movcore and Mcopro, has been established. The Mcopro prosthesis, which features an artificial annular structure, offers significant advantages in terms of reduced mobility of the operative level and peak stress of facet joint.


Assuntos
Análise de Elementos Finitos , Disco Intervertebral , Vértebras Lombares , Amplitude de Movimento Articular , Humanos , Vértebras Lombares/cirurgia , Vértebras Lombares/fisiopatologia , Disco Intervertebral/cirurgia , Disco Intervertebral/fisiopatologia , Fenômenos Biomecânicos , Desenho de Prótese , Substituição Total de Disco/métodos , Estresse Mecânico , Próteses e Implantes , Simulação por Computador , Modelos Biológicos , Articulação Zigapofisária/cirurgia , Articulação Zigapofisária/fisiopatologia
20.
J Biomech ; 169: 112131, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38739987

RESUMO

Cartilage endplates (CEPs) act as protective mechanical barriers for intervertebral discs (IVDs), yet their heterogeneous structure-function relationships are poorly understood. This study addressed this gap by characterizing and correlating the regional biphasic mechanical properties and biochemical composition of human lumbar CEPs. Samples from central, lateral, anterior, and posterior portions of the disc (n = 8/region) were mechanically tested under confined compression to quantify swelling pressure, equilibrium aggregate modulus, and hydraulic permeability. These properties were correlated with CEP porosity and glycosaminoglycan (s-GAG) content, which were obtained by biochemical assays of the same specimens. Both swelling pressure (142.79 ± 85.89 kPa) and aggregate modulus (1864.10 ± 1240.99 kPa) were found to be regionally dependent (p = 0.0001 and p = 0.0067, respectively) in the CEP and trended lowest in the central location. No significant regional dependence was observed for CEP permeability (1.35 ± 0.97 * 10-16 m4/Ns). Porosity measurements correlated significantly with swelling pressure (r = -0.40, p = 0.0227), aggregate modulus (r = -0.49, p = 0.0046), and permeability (r = 0.36, p = 0.0421), and appeared to be the primary indicator of CEP biphasic mechanical properties. Second harmonic generation microscopy also revealed regional patterns of collagen fiber anchoring, with fibers inserting the CEP perpendicularly in the central region and at off-axial directions in peripheral regions. These results suggest that CEP tissue has regionally dependent mechanical properties which are likely due to the regional variation in porosity and matrix structure. This work advances our understanding of healthy baseline endplate biomechanics and lays a groundwork for further understanding the role of CEPs in IVD degeneration.


Assuntos
Disco Intervertebral , Vértebras Lombares , Humanos , Vértebras Lombares/fisiologia , Disco Intervertebral/fisiologia , Pessoa de Meia-Idade , Masculino , Feminino , Porosidade , Adulto , Idoso , Glicosaminoglicanos/metabolismo , Fenômenos Biomecânicos , Cartilagem/fisiologia , Estresse Mecânico
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