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1.
Artigo em Inglês | MEDLINE | ID: mdl-37553841

RESUMO

Six-screw short-segment posterior fixation for thoracolumbar fractures, which involves intermediate screws at the fractured vertebrae has been proposed to reduce the rates of kyphosis recurrence and implant failure. Yet, little is known about the mechanisms and biomechanical responses by which intermediate screws at the fracture vertebrae enhance fixation strength. The objective of this study was to investigate the biomechanical properties that are associated with the augmentation of intermediate screws in relation to the severity of type A thoracolumbar fracture using finite element analysis. Short-segment stabilization models with or without augmentation screws at fractured vertebrae were established based on finite element model of moderate compressive fractures, severe compressive fractures and burst fractures. The spinal stiffness, stresses at the implanted hardware, and axial displacement of the bony defect were measured and compared under mechanical loading conditions. All six-screw stabilization showed a decreased range of motion in extension, lateral bending, and axial rotation compared to the traditional four-screw fixation models. Burst thoracolumbar fracture benefited more from augmentation of intermediate screws at the fracture vertebrae. The stress of the rod in six-screw models increased while decreased that of pedicle screws. Our results suggested that patients with more unstable fractures might achieve greater benefits from augmentation of intermediate screws at the fracture vertebrae. Augmentation of intermediate screws at the fracture vertebrae is recommended for patients with higher wedge-shaped or burst fractures to reduce the risk of hardware failure and postoperative re-collapse of injured vertebrae.

2.
Eur Spine J ; 32(10): 3561-3574, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37330937

RESUMO

PURPOSE: Adjacent segment degeneration (ASDeg) after anterior cervical discectomy and fusion (ACDF) seriously affects the long-term efficacy of the operation. Therefore, our team has done a lot of research on allograft intervertebral disc transplantation (AIDT) to prove its feasibility and safety. This study will compare the efficacy between AIDT and ACDF in the treatment of cervical spondylosis. METHODS: All patients who received ACDF or AIDT in our hospital from 2000 to 2016 and followed up for at least 5 years were recruited and divided into ACDF and AIDT groups. The clinical outcomes including functional scores and radiological data of both groups were collected and compared preoperatively and postoperatively at 1 week, 3 months, 6 months, 12 months, 24 months, 60 months and last follow-up. Functional scores included Japanese Orthopedic Association score (JOA), Neck Disability Index (NDI), Visual Analog Scale of Neck (N-VAS) and Arms (A-VAS) pain, the Short Form Health Survey-36 (SF-36) and imaging dates including digital radiographs in the lateral, hyperextension and flexion positions to assess the stability, sagittal balance and mobility of the cervical spine and magnetic resonance imaging (MRI) scans to assess the degeneration of adjacent segment. RESULTS: There were 68 patients with 25 in AIDT group and 43 in ACDF group. Satisfactory clinical results were obtained in both groups, but the long-term NDI score and N-VAS score in the AIDT group were better. The AIDT obtained the same stability and sagittal balance of the cervical spine as fusion surgery. The range of motion of adjacent segments can be restored to the preoperative level after transplantation, but this increases significantly after ACDF. There were significant differences in the superior adjacent segment range of motion (SROM) between two groups at 12 months (P = 0.039), 24 months (P = 0.035), 60 months (P = 0.039) and the last follow-up (P = 0.011). The inferior adjacent segment range of motion (IROM) and SROM had a similar trend in the two groups. The ratio value of the greyscale (RVG) of adjacent segments showed a downward trend. At the last follow-up, the RVG decreased more significantly in the ACDF group. At the last follow-up, there was a significant difference in the incidence of ASDeg between the two groups (P = 0.000). And the incidence of adjacent segment disease (ASDis) is 22.86% in the ACDF group. CONCLUSION: The allograft intervertebral disc transplantation may be as an alternative technique to traditional anterior cervical discectomy and fusion for the management of cervical degenerative diseases. For the more, the results showed it would improve cervical kinematics and reduce the incidence of adjacent segment degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Fusão Vertebral , Substituição Total de Disco , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/patologia , Seguimentos , Estudos Retrospectivos , Resultado do Tratamento , Disco Intervertebral/cirurgia , Discotomia/métodos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Vértebras Cervicais/patologia , Substituição Total de Disco/métodos , Aloenxertos/cirurgia , Fusão Vertebral/métodos
3.
Tissue Eng Part A ; 29(15-16): 424-438, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37279291

RESUMO

Intervertebral disc (IVD) degeneration (IDD) is a primary cause of low-back pain in people, which is associated with nucleus pulposus-derived mesenchymal stem cells (NPMSCs). In this study, the involvement of lipopolysaccharide (LPS) in the pyroptosis of NPMSCs was investigated. The effect of RADKPS on the pyroptosis of NPMSCs and the underlying mechanism behind the impact of RADKPS on the proliferative capacity of NPMSCs were also studied. Pyroptosis of NPMSCs was induced with 10 µg/mL LPS and its effects on the downstream signaling pathways were explored. The protective effect of RADKPS on NPMSCs under the action of LPS and its possible mechanism were explored, using different techniques such as immunohistochemical analysis, cell proliferation assay, quantitative real-time polymerase chain reaction (qPCR), and Western blot analysis. Accordingly, caspase1/p20/p10, a protein associated with pyroptosis, was found to be overexpressed in LPS-challenged NPMSCs, Furthermore, the qPCR results demonstrated that LPS promoted the expression of pyroptosis-related gene IL-1ß (p < 0.0001), while downregulating the expression of Sox-9 (p < 0.001), which was a gene associated with the extracellular matrix. The immunohistochemical results identified lowered extracellular signal-regulated kinase 1/2 (ERK1/2) expression and phosphorylated (p-)ERK1/2 in the degenerated IVD tissues. In this study, the influence of RADKPS on the proliferative ability of NPMSCs was evaluated using two-dimensional (2D) and three-dimensional (3D) cultures. It was noted that RADKPS promoted the proliferation of NPMSCs in 2D and 3D cultures. The findings of the Western blot experiments revealed that RADKPS inhibited the expression of pyroptosis-related proteins, while it upregulated the p-ERK1/2 (p < 0.001), RhoA (p < 0.01), collagen II (p < 0.01), and Sox-9 (p < 0.01), whereas ERK inhibitor PD98059 and RhoA signaling pathway inhibitor CCG-1423 inhibited their expression. These findings reveal to us that RADKPS hydrogel may protect NPMSCs from pyroptosis. It was also noted that cell proliferation-related signaling pathways may promote the proliferation of NPMSCs. The results revealed that RADKPS hydrogel could be used as a potential therapeutic approach for IDD. Impact Statement RADKPS inhibits the pyroptosis of NPMSCs and promotes the production of extracellular matrix, which has the potential of intervertebral disc biotherapy.


Assuntos
Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Humanos , Piroptose , Lipopolissacarídeos/farmacologia , Degeneração do Disco Intervertebral/metabolismo , Hidrogéis
4.
Mol Biol Rep ; 50(8): 6337-6347, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37310547

RESUMO

BACKGROUND: Degenerative disc disease(DDD)is one of the most important causes of low back pain (LBP). Programmed death of human nucleus pulposus mesenchymal stem cells (NPMSCs) plays an important role in the progression of DDD. Growth differentiation factor-5 (GDF-5) is a protein that promotes chondrogenic differentiation, and has been reported to slow the expression of inflammatory factors in nucleus pulposus cells. Compared with those in normal rats, MRI T2-weighted images show hypointense in the central nucleus pulposus region of the intervertebral disc in GDF-5 knockout rats. METHODS AND RESULTS: We aimed to evaluate the role of GDF-5 and Ras homolog family member A (RhoA) in NPMSCs. We used lipopolysaccharide (LPS) to simulate the inflammatory environment in degenerative disc disease, and performed related experiments on the effects of GDF-5 on NPMSCs, including the effects of pyroptosis, RhoA protein, and the expression of extracellular matrix components, and the effects of GDF-5, on NPMSCs. In addition, the effect of GDF-5 on chondroid differentiation of NPMSCs was included. The results showed that the addition of GDF-5 inhibited the LPS-induced pyroptosis of NPMSCs, and further analysis of its mechanism showed that this was achieved by activating the RhoA signaling pathway. CONCLUSION: These findings suggest that GDF-5 plays an important role in inhibiting the pyroptosis of NPMSCs and GDF-5 may have potential for degenerative disc disease gene-targeted therapy in the future.


Assuntos
Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Animais , Humanos , Ratos , Fator 5 de Diferenciação de Crescimento/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/terapia , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Núcleo Pulposo/metabolismo , Piroptose , Proteína rhoA de Ligação ao GTP/metabolismo , Transdução de Sinais
5.
Zhongguo Gu Shang ; 36(5): 487-9, 2023 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-37211944

RESUMO

OBJECTIVE: To explore the technical aspects of the accuracy of cervical pedicle screw placement with O-arm guidance. METHODS: The clinical data of 21 patients who underwent cervical pedicle screw fixation by O-arm real-time guidance from December 2015 to January 2020 were analyzed retrospectively. There were 15 males and 6 females, aged from 29 to 76 years old with an average of (45.3±11.5) years. The postoperative CT scan was utilized to evaluate the placement of the pedicle screw and classified according to the Gertzbein and Robbins classification. RESULTS: A total of 132 pedicle screws were implanted in 21 patients, 116 at C3-C6 and 16 at C1 and C2. According to Gertzbein & Robbins classification, the overall breach rates were found to be 11.36% (15/132) with 73.33% (11 screws) Grade B, 26.67% (4 screws) Grade C, and no Grade D or E screw breaches. There were no pedicle screw placement related complications at final follow-up. CONCLUSION: The application of O-arm real-time guidance technology can make cervical pedicle screw placement reliable. High accuracy and better intra-operative control can increase surgeon's confidence in using cervical pedicle instrumentation. Considering the high-risk nature of anatomical area around cervical pedicle and the possibility of catastrophic complications, the spine surgeon should have sufficient surgical skills, experience, ensures stringent verification of the system, and never relies solely on the navigation system.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Cirurgia Assistida por Computador , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Imageamento Tridimensional , Tomografia Computadorizada por Raios X
6.
Immun Inflamm Dis ; 11(5): e865, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37249300

RESUMO

BACKGROUND: Excessive oxidative stress has been accepted as one of the critical factors for intervertebral disc degeneration (IDD), which is associated with low back pain (LBP). Fisetin (Fis) is a bioactive flavonoid that possesses strong bioactive activity. In present study, we aimed to illuminate the role of Fis on nucleus pulposus mesenchymal stem cells (NPMSCs). METHODS: NPMSCs were isolated and cultured from rat NP tissues and identified by flow cytometry and multilinear differentiation. The cytotoxicity of Fis, EX-527, and hydrogen peroxide (H2 O2 ) on NPMSCs was validated using Cell Counting Kit-8 tests. Cell apoptosis was tested by flow cytometry and TUNEL assay. Inflammatory mediators were assessed by Elisa tests, RT-PCR. Extracellular matrix (ECM) metabolism was measured by Western blot analysis and RT-qPCR. The expression of the SIRT1 was evaluated by Western blot analysis. RESULTS: NPMSCs were successfully isolated and cultured from rat NP tissues, and it has been identified by flow cytometry and multilinear differentiation. The results showed that Fis attenuated H2 O2 -induced apoptosis, inflammation, and ECM degradation of NPMSCs. Moreover, the above protective effects of Fis can be inhibited by EX-527, a unique SIRT1 inhibitor, indicating that SIRT1 may involve in the mechanism of Fis in protecting NPMSCs from oxidative stress. CONCLUSIONS: As a natural compound with little cytotoxicity on NPMSCs, Fis alleviate H2 O2 -induced apoptosis, inflammation, and ECM degradation by suppressing oxidative stress, this finding may add the theoretical basis for research on new treatment of IDD based on NPMSCs.


Assuntos
Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Animais , Ratos , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Estresse Oxidativo , Ratos Sprague-Dawley , Sirtuína 1/genética , Sirtuína 1/metabolismo
7.
Zhongguo Gu Shang ; 35(11): 1104-8, 2022 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-36415200

RESUMO

Anterior cervical discectomy and fusion (ACDF) has achieved good clinical results since it was used in clinic, and is considered as the gold standard for the treatment of cervical spondylosis. However, more and more attention has been paid to adjacent segment degeneration(ASDeg) after fusion, and the debate about its pathogenesis is mainly focused on the bio-machanical stress changes of adjacent segments caused by fusion and the result of the natural aging process. The occurrence of ASDeg after fusion seriously affect the med-and long-term outcome of surgery, and some patients even need secondary surgery. In order to reduce or even avoid the occurrence of ASDeg, many new techniques have emerged in clinic, such as artificial disc replacement with preservation of motor segments, emerging cell transplantation technology and so on, but the clinical effect still needs to be confirmed by a large number of studies. Therefore, finding the risk factors of ASDeg after fusion is of great significance for fusion surgery on the clinical work. At present, there is still no unified overview of the research on the risk factors of ASDeg. This article will review the research progress and corresponding countermeasures of the risk factors of ASDeg after ACDF, in order to guide the clinical application.


Assuntos
Espondilose , Substituição Total de Disco , Humanos , Fatores de Risco , Discotomia/efeitos adversos , Espondilose/cirurgia
8.
Mol Med Rep ; 26(3)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35856417

RESUMO

Intervertebral disc degeneration (IDD) creates a hostile environment with high osmotic pressure, high mechanical stress, hypoxia and a low pH, where cytokines such as TNF­α and IL­1ß are highly expressed. The degenerating intervertebral disc has high local expression of monocyte chemoattractant protein­1 (MCP­1), which is associated with the degree of degeneration. However, there are a few reports on the influence of MCP­1 on nucleus pulposus­derived stem cells (NPSCs). In the present study, a significant upregulation of MCP­1 was observed in NPSCs cultured in vitro with pro­inflammatory cytokines. MCP­1 significantly inhibited the migration and proliferation of NPSCs in a dose­dependent manner as detected via Cell Counting Kit­8, wound healing and Transwell assays. Western blotting and histological analysis demonstrated that MCP­1 significantly reduced chondrogenic NPSC differentiation. Reverse transcription­quantitative PCR and western blotting revealed that C­C chemokine receptor type 2 (CCR2) mRNA and protein expression levels were significantly enhanced by MCP­1. Furthermore, MCP­1 significantly inhibited the migration, differentiation and proliferation of NPSCs, which was effectively reversed by blocking CCR2 with the inhibitor RS504393. Overall, these results demonstrated that MCP­1 may contribute to the inhibition of chondrogenic NPSC differentiation via MCP­1/CCR2 chemotaxis signals, providing a potential therapeutic target for IDD.


Assuntos
Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , Núcleo Pulposo , Diferenciação Celular/genética , Citocinas/metabolismo , Humanos , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Células-Tronco Mesenquimais/metabolismo , Núcleo Pulposo/metabolismo , Receptores CCR2/genética
9.
Biomater Sci ; 10(18): 5134-5145, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-35820128

RESUMO

Objective: the aim of this study was to investigate whether the functionalized self-assembling peptide hydrogel RADKPS is safe and effective for regenerative repair of degenerative intervertebral discs. Methods: an in vitro degenerative model of human nucleus pulposus cells was constructed by serum starvation culture, and their proliferation, apoptosis and viability were examined after three-dimensional culture with the RADKPS hydrogel. An in vivo degenerative model of the rabbit intervertebral disc was constructed by annulus fibrosus puncture, and the degeneration of the intervertebral disc was evaluated by imaging, histology, immunohistochemistry, and biomechanics after RADKPS hydrogel intervention. Results: through in vitro cell experiments it is shown that human degenerated nucleus pulposus cells after three-dimensional culture with the RADKPS hydrogel still exhibited better proliferation, viability, and low apoptosis rate. Through in vivo animal experiments we found that rabbit degenerated intervertebral discs intervened with the RADKPS hydrogel had higher water content, better histological morphology, more extracellular matrix synthesis, and better biomechanical properties. It is demonstrated that the RADKPS hydrogel may initiate the endogenous repair process through the sustained recruitment and enrichment of nucleus pulposus progenitor cells. Conclusion: it is verified from both in vitro cellular experiments and in vivo animal experiments that the regenerative repair effect of RADKPS, a functionalized self-assembling peptide hydrogel, on degenerated intervertebral discs is safe and effective. It is shown that it would be a new therapeutic approach for the regenerative repair action of intervertebral discs.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animais , Modelos Animais de Doenças , Humanos , Hidrogéis/química , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Peptídeos/química , Peptídeos/farmacologia , Coelhos
10.
Stem Cells Transl Med ; 11(5): 490-503, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35427416

RESUMO

The treatment of intervertebral disc degeneration (IVDD) is still a huge challenge for clinical updated surgical techniques and basic strategies of intervertebral disc regeneration. Few studies have ever tried to combine surgery and cell therapy to bridge the gap between clinical and basic research. A prospective clinical study with a 72-month follow-up was conducted to assess the safety and feasibility of autologous discogenic cells transplantation combined with discectomy in the treatment of lumbar disc herniation (LDH) and to evaluate the regenerative ability of discogenic cells in IVDD. Forty patients with LDH who were scheduled to have discectomy enrolled in our study and were divided into the observed group (transplantation of autologous discogenic cells after discectomy) and control group (only-discectomy). Serial MRI and X-ray were used to evaluate the degenerative extent of index discs, and clinical scores were used to determine the symptomatic improvement. No adverse events were observed in the observed group, and seven patients in the control group underwent revisions. Both groups had significant improvement of all functional scores post-operatively, with the observed group improving more considerably at 36-month and 72-month follow-up. The height and water content of discs in both groups decreased significantly since 36 months post-op with the control group decreased more obviously. Discectomy combined with autologous discogenic cells transplantation is safe and feasible in the treatment of LDH. Radiological analysis demonstrated that discogenic cells transplantation could slow down the further degeneration of index discs and decrease the complications of discectomy.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Discotomia/efeitos adversos , Discotomia/métodos , Estudos de Viabilidade , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Estudos Prospectivos , Resultado do Tratamento
12.
BMC Musculoskelet Disord ; 22(1): 914, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717595

RESUMO

BACKGROUND: To reduce incision complications, minimally invasive operative approaches for treatment with acute Achilles tendon rupture have been developed, such as Mini-open repair and percutaneous repair. Which technique is the better surgical option? In the present study, we compared the two surgical procedures- modified Mini-open repair versus percutaneous repair-in the treatment of acute Achilles tendon rupture. METHODS: From January 2016 to November 2018, 68 matched patients with acute Achilles tendon rupture were divided into treatment group (Mini-open with modified Ma-Griffith technique) and control group (the Ma-Griffith technique). The patients were then treated with different surgical techniques and followed up for no less than 24 months, and the functional outcome scores and complications were retrospectively evaluated. RESULTS: The mean follow-up time in Mini-open repair group was 29.0±2.9 months, and that in control group was 27.9±2.9 months (P=0.147). The Mini-open repair group showed reliably higher American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score and Achilles tendon Total Rupture Score (ATRS) than the control group in functional assessment (95.0±3.8 vs. 92.3±5.3, P=0.000; 93.8±3.8 vs. 90.9±4.5,P=0.000). There was no cases of sural nerve injury in Mini-open repair group, whereas the percutaneous repair group had 5 cases of the same (P=0.027). No significant differences were found in the calf circumference (32.3±3.9 vs. 31.8±3.6) (P=0.564), range of motion of the ankle (51.3±4.8 vs. 50.5±4.2, P=0.362), or wound complications (34/0 vs. 34/0) (P=1.000) between the two groups at the end of the follow-up time. However, the percutaneous repair group had a shorter average operating time (23.1±5.2 min) than that of the Mini-open repair group (27.7±4.3 min) (P=0.000). CONCLUSIONS: Acute Achilles tendon ruptures may be treated successfully with a new Mini-open repair system or percutaneous repair technique. However, the Mini-open repair system may represent a superior surgical option, since it offers advantages in terms of direct visual control of the repair, AOFAS Ankle-Hindfoot Score, Achilles tendon Total Rupture Score and risk of sural nerve palsy. STUDY DESIGN: Case-control studies, Level of evidence, 3.


Assuntos
Tendão do Calcâneo , Procedimentos Ortopédicos , Tendão do Calcâneo/cirurgia , Humanos , Procedimentos Ortopédicos/efeitos adversos , Estudos Retrospectivos , Ruptura/cirurgia , Resultado do Tratamento
13.
Arch Osteoporos ; 16(1): 93, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34105042

RESUMO

INTRODUCTION: Surgical treatments are usually preferred in patients with Kümmell's disease since it represents a failure of conservative treatment for osteoporotic vertebral compression fracture without evidence of spontaneous healing. However, the risk of postoperative refractures is much higher in patients with glucocorticosteroid-induced osteoporosis (GIOP) than in those with primary osteoporosis, possessing a therapeutic challenge and dilemma to orthopaedic surgeons. CASE REPORT: We described a rare cluster phenomenon of vertebral refractures in a patient with GIOP subsequent to segmental internal fixation for the initial management of glucocorticosteroid-induced Kümmell's disease, and a review of the literature. CONCLUSION: Our patient illustrates that clinicians should be aware of the significant management dilemma and possible disastrous outcome after surgical interventions for glucocorticosteroid-induced Kümmell's disease and, thus, pay much more attention to comprehensive perioperative antiosteoporotic medications for patients with GIOP in current medical treatment.


Assuntos
Fraturas por Compressão , Parafusos Pediculares , Fraturas da Coluna Vertebral , Vertebroplastia , Cimentos Ósseos , Humanos , Resultado do Tratamento
14.
Oxid Med Cell Longev ; 2021: 6492879, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33833850

RESUMO

Inflammation plays a key role in intervertebral disc degeneration (IDD). The association between inflammation and endoplasmic reticulum (ER) stress has been observed in many diseases. However, whether ER stress plays an important role in IDD remains unclear. Therefore, this study is aimed at investigating the expression of ER stress in IDD and at exploring the underlying mechanisms of IDD, ER stress, and inflammation. The expression of ER stress was activated in nucleus pulposus cells from patients who had IDD (D-NPCs) compared with patients without IDD (N-NPCs); and both the proliferation and synthesis capacity were decreased by inducer tunicamycin (Tm) and proinflammatory cytokines. Pretreatment of NPCs with 4-phenyl butyric acid (4-PBA) prevented the inflammatory cytokine-induced upregulation of unfolded protein response- (UPR-) related proteins and recovered cell synthetic ability. Furthermore, proinflammatory cytokine treatment significantly upregulated the expression of inositol-requiring protein 1 (IRE1-α) and protein kinase RNA-like ER kinase (PERK), but not activating transcription factor 6 (ATF6). Finally, knockdown of IRE1-α and PERK also restored the biological activity of NPCs. Our findings identified that IRE1-α and PERK might be the potential targets for IDD treatment, which may help illustrate the underlying mechanism of ER stress in IDD.


Assuntos
Endorribonucleases/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Resposta a Proteínas não Dobradas , eIF-2 Quinase/metabolismo , Adolescente , Adulto , Anti-Inflamatórios/farmacologia , Butilaminas/farmacologia , Células Cultivadas , Feminino , Humanos , Interleucina-1beta/farmacologia , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/efeitos dos fármacos , Núcleo Pulposo/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Tunicamicina/farmacologia
15.
J Mater Sci Mater Med ; 31(10): 88, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044713

RESUMO

In the present study, the microstructure, mechanical properties, corrosion behavior, wettability, haemocompatibility, and cytocompatibility of the as-cast and as-rolled biodegradable Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca have been systematically investigated to evaluate their feasibility as potential biodegradable materials. The results demonstrated that the Zn-1Mg-0.1Ca have significantly improved mechanical properties, with the yield strength (YS), ultimate tensile strength (UTS), and elongation of as-rolled Zn-1Mg-0.1Ca are (209.04 ± 28.31) MPa, (331.51 ± 40.06) MPa, and (35.43 ± 3.53)%, respectively. Wettability test results demonstrated that the Zn-1Mg-0.1Ca and Zn-1Mg-0.5Ca have hydrophilic surfaces that can enhance cell responses and tissue-implant interactions. The haemocompatibility evaluation showed that the hemolysis ratio of Zn-1Mg-0.1Ca have a low hemolysis ratio of 0.6%; the platelets remain sphere morphology and are not activated. High cell viability indicates the cytocompatibility of the as-rolled Zn-1Mg-0.1Ca alloy. The Zn-1Mg-0.1Ca alloy can be considered as new suitable biodegradable Zn-based alloys for further biomedical applications.


Assuntos
Materiais Biocompatíveis/química , Cálcio/química , Magnésio/química , Zinco/química , Células 3T3 , Implantes Absorvíveis , Ligas , Animais , Linhagem Celular Tumoral , Corrosão , Eletroquímica , Hemólise , Humanos , Técnicas In Vitro , Teste de Materiais , Camundongos , Adesividade Plaquetária , Pressão , Desenho de Prótese , Estresse Mecânico , Temperatura , Resistência à Tração , Molhabilidade , Difração de Raios X
16.
Folia Histochem Cytobiol ; 58(3): 227-234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936927

RESUMO

INTRODUCTION: Intervertebral disc degeneration (IDD) is one of the major causes of low back pain (LBP) which seriously affects health and normal physical activity. Recombinant human tumor necrosis factor-a (TNF-a) induced protein 6 (rhTSG-6) has been reported to have therapeutic effects on a variety of inflammatory diseases, but the effect and mechanism of rhTSG-6 action in IDD are not fully understood. The present study was aimed to explore the functional role of rhTSG-6 in interleukin (IL)-1b-induced nucleus pulposus (NP) cell model. MATERIALS AND METHODS: Experimental human NP cells were isolated from the patients with idiopathic scoliosis and treated with culture medium containing IL-1b (10 ng/mL) for 24 hours to induce extracellular matrix degradation and apoptosis, simulating an IDD model in vitro. The viability of NP cells was analyzed by the CCK-8 assay. The relevant mRNA and protein levels were measured by RT-qPCR and western blot. The apoptosis of NP cells was determined by flow cytometry analysis and western blot. RESULTS: Compared with the NP cells without IL-1b treatment, IL-1b caused approximately 70% reduction in the viability of NP cells, while RhTSG-6 partly increased the decrease of IL-1b on cell viabilities. Moreover, treatment with rhTSG-6 considerably attenuated the upregulation of extracellular matrix (ECM)-catabolic factors (MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5), and increased the downregulation of ECM-anabolic factor (collagen II) in NP cells induced by IL-1b, indicating that ECM degradation was suppressed. Furthermore, rhTSG-6 also protected NP cells from IL-1b-induced apoptosis. Mechanically, rhTSG-6 inhibited the activation of members of mitogen-activated protein kinase (MAPK) pathway by blocking the phosphorylation of p38, c-Jun N-terminal kinase (JNK) and ERK in IL-1b-induced NP cells. CONCLUSIONS: RhTSG-6 can attenuate ECM degradation and apoptosis in IL-1b-induced NP cells by inhibiting the p38, JNK and ERK pathways, which may contribute to its potential application in the therapy of IDD.


Assuntos
Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/farmacologia , Matriz Extracelular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Núcleo Pulposo/metabolismo , Proteínas Recombinantes/farmacologia , Adolescente , Adulto , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Interleucina-1beta/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , MAP Quinase Quinase 4/metabolismo , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , Escoliose/patologia , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Chin J Traumatol ; 23(5): 258-264, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32771244

RESUMO

OBJECTIVE: Fragment injury is a type of blast injury that is becoming more and more common in military campaigns and terrorist attacks. Numerical simulation methods investigating the formation of natural fragments and injuries to biological targets are expected to be developed. METHODS: A cylindrical warhead model was established and the formation process of natural fragments was simulated using the approach of tied nodes with failure through the explicit finite element (FE) software of LS-DYNA. The interaction between the detonation product and the warhead shell was simulated using the fluid-structure interaction algorithm. A method to simulate the injury of natural fragments to a biological target was presented by transforming Lagrange elements into smooth particle hydrodynamics (SPH) particles after the natural fragments were successfully formed. A computational model of the human thorax was established to simulate the injury induced by natural fragments by the node-to-surface contact algorithm with erosion. RESULTS: The discontinuous velocities of the warhead shell at different locations resulted in the formation of natural fragments with different sizes. The velocities of natural fragments increased rapidly at the initial stage and slowly after the warhead shell fractured. The initial velocities of natural fragments at the central part of the warhead shell were the largest, whereas those at both ends of the warhead shell were the smallest. The natural fragments resulted in bullet holes that were of the same shape as that of the fragments but slightly larger in size than the fragments in the human thorax after they penetrated through. Stress waves propagated in the ribs and enhanced the injury to soft tissues; additionally, ballistic pressure waves ahead of the natural fragments were also an injury factor to the soft tissues. CONCLUSION: The proposed method is effective in simulating the formation of natural fragments and their injury to biological targets. Moreover, this method will be beneficial for simulating the combined injuries of natural fragments and shock waves to biological targets.


Assuntos
Traumatismos por Explosões/etiologia , Simulação por Computador , Modelos Anatômicos , Traumatismos Torácicos/etiologia , Traumatismos por Explosões/complicações , Análise de Elementos Finitos , Ondas de Choque de Alta Energia/efeitos adversos , Humanos
18.
BMC Musculoskelet Disord ; 21(1): 540, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787885

RESUMO

BACKGROUND: Kashin-Beck disease (KBD) is a disabling osteoarticular disease involving growth and joint cartilage. Early diagnosis can effectively prevent the progress of the disease. However, the early diagnosis of it is still very difficult. Our aim was to study the knee joint lesions of a rat KBD model using ultra-high field magnetic resonance imaging (MRI) and compare it with X-ray imaging to analyze the possible MRI manifestations of KBD, and to further explore ways to determine the pathological damage of KBD in the early stage. METHODS: A total of 96 Wistar rats were selected and randomly divided into 4 groups: normal diet (Group A), KBD-affected diet (Group B), normal diet+T-2 toxin (Group C), and KBD-affected diet+T-2 toxin (Group D). T-2 toxin was administered at a dose of 0.1 mg/kg/day. In the 4th week, 8th week, and 12th week, eight rats randomly selected in each group were sacrificed by cervical dislocation after undergoing X-ray and 7.0 T MRI imaging, and then knee joints were harvested, sliced, and subjected to hematoxylin-eosin (H&E) staining. RESULTS: Characteristic image changes including of continuity interruption and early closure and fusion of epiphyseal plates were observed on T1WI in rat model of KBD. The total necrosis rates in the H&E stain of group A to group D were 4.35, 52.38, 33.3, and 73.68%, respectively. The positive rate of image change under 7.0 T MRI was 0.833 VS. that under X-ray was 0.33 (P = 0.001). CONCLUSIONS: MRI at 7.0 T is highly sensitive to the early pathological changes of the epiphysis, epiphyseal plate, and metaphyseal end, which can improve imaging positive rate of KBD and decrease the rate of missed diagnosis. This imaging modality can be used for research on early joint lesions and for early diagnosis of KBD.


Assuntos
Doença de Kashin-Bek , Animais , Epífises/diagnóstico por imagem , Lâmina de Crescimento/diagnóstico por imagem , Doença de Kashin-Bek/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ratos , Ratos Wistar
19.
Int J Mol Med ; 46(3): 1074-1084, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705163

RESUMO

Intervertebral disc degeneration (IDD) is a condition involving disruption of the bone tissue distribution. Nucleus pulposus mesenchymal stem cells (NPMSCs) and Sirtuin 1 (SIRT1) play important roles in bone diseases, therefore the aim of the present study was to evaluate the roles of SIRT1 and NPMSCs in IDD. First, NPMSCs were harvested from patients with IDD. Then, the NPMSCs were treated with a SIRT activator, and monocyte chemoattractant protein 1 (MCP1) and chemokine receptor 2 (CCR2) inhibitors. Indices related to NPMSC growth, proliferation, differentiation and apoptosis were measured. Subsequently, IDD rat models were established and were transfected with NPMSCs overexpressing SIRT1. NPMSC apoptosis and cartilage differentiation were detected in the rat IDD model. SIRT1 expression was found to be decreased, and the expression of MCP1 and CCR2 increased in NPMSCs of patients with IDD. The upregulation of SIRT1 and the downregulation of the MCP1/CCR2 axis promoted cartilage differentiation and reduced the number of apoptotic NPMSCs. Furthermore, MCP1 reversed the progression of the cartilage differentiation of NPMSCs and the inhibition of NPMSC apoptosis induced by SIRT1 overexpression. Moreover, the transplantation of rat NPMSCs overexpressing SIRT1 relieved IDD in rats. Therefore, SIRT1 overexpression improved cartilage differentiation and reduced the apoptosis of NPMSCs by inactivating the MCP1/CCR2 axis, thus attenuating IDD in rats.


Assuntos
Quimiocina CCL2/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais , Sirtuína 1/metabolismo , Idoso , Animais , Apoptose , Cartilagem/metabolismo , Cartilagem/patologia , Diferenciação Celular , Células Cultivadas , Condrogênese , Feminino , Humanos , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Ratos Sprague-Dawley , Sirtuína 1/genética , Regulação para Cima
20.
BMC Musculoskelet Disord ; 21(1): 333, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471475

RESUMO

BACKGROUND: The anteroposterior view of the lumbar plain radiograph (AP-LPR) was chosen as the original and first radiographic tool to determine and classify lumbosacral transitional vertebra with morphological abnormality (MA-LSTV) according to the Castellvi classification. However, recent studies found that AP-LPR might not be sufficient to detect or classify MA-LSTV correctly. The present study aims to verify the reliability of AP-LPR on detecting and classifying MA-LSTV types, taking coronal reconstructed CT images (CT-CRIs) as the gold criteria. METHODS: Patients with suspected MA-LSTVs determined by AP-LPR were initially enrolled. Among them, those who received CT-CRIs were formally enrolled to verify the sensitivity of AP-LPR on detecting and classifying MA-LSTV types according to the Castellvi classification principle. RESULTS: A total of 298 cases were initially enrolled as suspected MA-LSTV, among which 91 cases who received CT-CRIs were enrolled into the final study group. All suspected MA-LSTVs were verified to be real MA-LSTVs by CT-CRIs. However, 35.2% of the suspected MA-LSTV types judged by AP-LPR were not consistent with the final types judged by CT-CRIs. Two suspected type IIIa and 20 suspected type IIIb MA-LSTVs were verified to be true, while 9 of 39 suspected type IIa, 9 and 3 of 17 suspected type IIb, and 11 of 13 suspected type IV MA-LSTVs were verified to truly be type IIIa, IIIb, IV and IIIb MA-LSTVs by CT-CRIs, respectively. Incomplete joint-like structure (JLS) or bony union structure (BUS) and remnants of sclerotic band (RSB) between the transverse process (TP) and sacrum were considered to be the main reasons for misclassification. CONCLUSION: Although AP-LPR could correctly detect MA-LSTV, it could not give accurate type classification. CT-CRIs could provide detailed information between the TP and sacrum area and could be taken as the gold standard to detect and classify MA-LSTV.


Assuntos
Vértebras Lombares/anormalidades , Anormalidades Musculoesqueléticas/diagnóstico , Sacro/anormalidades , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Vértebras Lombares/patologia , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Radiografia , Reprodutibilidade dos Testes , Sacro/diagnóstico por imagem , Sacro/patologia , Adulto Jovem
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