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BACKGROUND: Giant cell tumour (GCT) of the bone is a rare, invasive benign bone tumour, which typically originates in the metaphyseal ends of long bones and rarely in the spine. Here, we report a rare case of recurrent GCT of the thoracic vertebra, which was managed by three-level total en bloc spondylectomy (TES) after denosumab therapy. CASE PRESENTATION: A 50-year-old woman presented with a 2-month history of progressive lower back pain. Magnetic resonance imaging revealed destruction of the T11 vertebra and a soft tissue mass. The patient underwent tumour resection. Computed tomography at the 2-year follow-up revealed relapse of the resected tumour, which had spread to the T12 vertebral body. Subsequently, denosumab therapy was administered to the patient for 1 year. The growth of the tumour was controlled, and its boundary line was clear. Thereafter, TES for the T10-T12 vertebrae was performed, and spinal reconstruction was completed through a one-stage single posterior approach. The patient's condition improved postoperatively, and no evidence of recurrence of GCT of the bone or spinal deformity was observed at the 32-month follow-up. CONCLUSIONS: Denosumab therapy contributed to tumour regression. Three-level TES may be an effective and feasible strategy for managing large recurrent GCTs of the spine after denosumab therapy.
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Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Neoplasias da Coluna Vertebral/tratamento farmacológico , Neoplasias da Coluna Vertebral/cirurgia , Feminino , Seguimentos , Tumor de Células Gigantes do Osso/diagnóstico por imagem , Humanos , Dor Lombar , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
OBJECTIVE: Patients undergoing long-segment fusions from the lower thoracic (LT) spine to the sacrum for adult spinal deformity (ASD) correction are at risk for proximal junctional kyphosis (PJK). One mechanism of PJK is fracture of the upper instrumented vertebra (UIV) or higher (UIV+1), which may be related to bone mineral density (BMD). Because Hounsfield units (HUs) on CT correlate with BMD, the authors evaluated whether HU values were correlated with PJK after long fusions for ASD. METHODS: The authors performed a retrospective study of patients older than 50 years who had undergone ASD correction from the LT spine to the sacrum in the period from October 2007 to January 2018 and had a minimum 2-year follow-up. Demographic and spinopelvic parameters were measured. HU values were measured on preoperative CT at the UIV, UIV+1, and UIV+2 (2 levels above the UIV) levels and were assessed for correlations with PJK. RESULTS: The records of 127 patients were reviewed. Fifty-four patients (19 males and 35 females) with a mean age of 64.91 years and mean follow-up of 3.19 years met the study inclusion criteria; there were 29 patients with PJK and 25 patients without. There was no statistically significant difference in demographics or follow-up between these two groups. Neither was there a difference between the groups with regard to postoperative pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), PI minus LL (PI-LL), thoracic kyphosis (TK), or sagittal vertical axis (SVA; all p > 0.05). Postoperative pelvic tilt (p = 0.003) and T1 pelvic angle (p = 0.014) were significantly higher in patients with PJK than in those without. Preoperative HUs at UIV, UIV+1, and UIV+2 were 120.41, 124.52, and 129.28 in the patients with PJK, respectively, and 152.80, 155.96, and 160.00 in the patients without PJK, respectively (p = 0.011, 0.02, and 0.018). Three receiver operating characteristic (ROC) curves for preoperative HU values at the UIV, UIV+1, and UIV+2 as a predictor for PJK were established, with areas under the ROC curve of 0.710 (95% CI 0.574-0.847), 0.679 (95% CI 0.536-0.821), and 0.681 (95% CI 0.539-0.824), respectively. The optimal HU value by Youden index was 104 HU at the UIV (sensitivity 0.840, specificity 0.517), 113 HU at the UIV+1 (sensitivity 0.720, specificity 0.517), and 110 HU at the UIV+2 (sensitivity 0.880, specificity 0.448). CONCLUSIONS: In patients undergoing long-segment fusions from the LT spine to the sacrum for ASD, PJK was associated with lower HU values on CT at the UIV, UIV+1, and UIV+2. The measurement of HU values on preoperative CTs may be a useful adjunct for ASD surgery planning.
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Cifose/cirurgia , Vértebras Lombares/cirurgia , Sacro/cirurgia , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Cifose/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sacro/diagnóstico por imagem , Fusão Vertebral/tendências , Vértebras Torácicas/diagnóstico por imagem , Fatores de TempoRESUMO
PURPOSE: Adamantinoma is a low-grade primary malignant bone tumour with slow growth and local recurrence. Its occurrence in the spine is extremely rare, particularly with multilevel involvement. This paper wants to present the first case involving a patient with recurrent thoracolumbar spinal adamantinoma, who underwent a successful three-level spondylectomy for en bloc resection. METHODS: A 24-year-old man with osteolytic masses of T11 and T12 vertebral bodies was performed curettage by a posterior approach in 2008. The pathology report showed the excised neoplasm was a rare adamantinoma. This patient underwent a tumorectomy again because of its local recurrence nearly 3 years later. In 2012, it was unfortunately revealed that the excised tumour had relapsed and had spread to the L1 vertebral body. Due to its repeated recurrence and aggressive lesion, total en bloc spondylectomy (TES) for this malignant tumour was thought to be the best option for preventing repeated recurrence and possible cure. TES for T11-L1 thoracolumbar spine was performed and spinal reconstruction was completed with instrumentation and a titanium mesh cage through a one-stage single posterior approach. RESULTS: After three-level TES, neurological deficits of the patient demonstrated good recovery and no evidence of adamantinoma recurrence or deformity was found at 2-year follow-up. CONCLUSIONS: This is the first case involving multilevel thoracolumbar spinal adamantinoma with repeated recurrence to be successfully treated by three-level TES by a single posterior approach.
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Adamantinoma/cirurgia , Vértebras Lombares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Ortopédicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Humanos , Masculino , Procedimentos Ortopédicos/instrumentação , Próteses e Implantes , Procedimentos de Cirurgia Plástica/instrumentação , Adulto JovemRESUMO
OBJECTIVE: Generally, anterior lumbar interbody fusion (ALIF) was believed superior to transforaminal lumbar interbody fusion (TLIF) in induction of fusion. However, many studies have reported comparable results in lumbosacral fusion rate between the two approaches. This study aimed to evaluate the realistic lumbosacral arthrodesis rates following ALIF and TLIF in patients with degenerative spondylolisthesis as measured by CT and radiology. METHODS: Ninety-six patients who underwent single-level L5-S1 fusion through ALIF (n = 48) or TLIF (n = 48) for degenerative spondylolisthesis at the Spine Center, University of California San Francisco, between October 2014 and December 2017 were retrospectively evaluated. Fusion was independently evaluated and categorized as solid fusion, indeterminate fusion, or pseudarthroses by two radiologists using the modified Brantigan-Steffee-Fraser (mBSF) grade. Clinical data on sex, age, body mass index, Meyerding grade, smoking status, follow-up times, complications, and radiological parameters including disc height, disc angle, segmental lordosis, and overall lumbar lordosis were collected. The fusion results and clinical and radiographic data were statistically compared between the ALIF and TLIF groups by using t-test or chi-square test. RESULTS: The mean follow-up period was 37.5 (ranging from 24 to 51) months. Clear, solid radiographic fusions were higher in the ALIF group compared with the TLIF group at the last follow-up (75% vs 47.9%, p = 0.006). Indeterminate fusion occurred in 20.8% (10/48) of ALIF cases and in 43.8% (21/48) of TLIF cases (p = 0.028). Radiographic pseudarthrosis was not significantly different between the TLIF and ALIF groups (16.7% vs 8.3%; p = 0.677). In subgroup analysis of the patients without bone morphogenetic protein (BMP), the solid radiographic fusion rate was significantly higher in the ALIF group than that in the TLIF group (78.6% vs 45.5%; p = 0.037). There were no differences in sex, age, body mass index, Meyerding grade, smoking status, or follow-up time between the two groups (p > 0.05). The ALIF group had more improvement in disc height (7.8 mm vs 4.7 mm), disc angle (5.2° vs 1.5°), segmental lordosis (7.0° vs 2.5°), and overall lumbar lordosis (4.7° vs 0.7°) compared with the TLIF group (p < 0.05). Overall complication rates were similar between the TLIF and ALIF groups (10.4% vs 8.33%; p > 0.999). CONCLUSIONS: With a minimum 2-year radiographic analysis of arthrodesis at lumbosacral level by radiologists, the rate of solid radiographic fusions was higher in the ALIF group compared with the TLIF group, whereas the TLIF group had a higher rate of indeterminate fusion. Radiographic pseudarthrosis did not differ significantly between the TLIF and ALIF groups.
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Lordose , Fusão Vertebral , Espondilolistese , Humanos , Lordose/cirurgia , Seguimentos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Overcorrection in adult spinal deformity (ASD) surgery may lead to proximal junctional kyphosis (PJK) because of posterior spinal displacement. The aim of this paper is to determine if the L1 position relative to the gravity line (GL) is associated with PJK. METHODS: ASD patients fused from the lower thoracic spine to sacrum by 4 spine surgeons at our hospital were retrospectively studied. Lumbar-only and upper thoracic spine fusions were excluded. Spinopelvic parameters, the L1 plumb line (L1PL), L1 distance to the GL (L1-GL), and Roussouly type were measured. RESULTS: One hundred fourteen patients met inclusion criteria (63 patients with PJK, 51 without). Mean age and follow up was 65.51 and 3.39 years, respectively. There was no difference between the PJK and the non-PJK groups in baseline demographics, pre-operative and immediate post-operative pelvic incidence-lumbar lordosis mismatch, sagittal vertical axis, or coronal Cobb. The immediate postoperative L1-GL was -7.24 cm in PJK and -3.45 cm in non-PJK (P < 0.001), L1PL was 1.71 cm in PJK and 3.07 cm in non-PJK (P = 0.004), and PT (23.76° vs 18.90°, P = 0.026) and TK (40.56° vs 31.39°, P < 0.001) were larger in PJK than in non-PJK. After univariate and multivariate analyses, immediate postoperative TK and immediate postoperative L1-GL were independent risk factors for PJK without collinearity. CONCLUSIONS: A dorsally displaced L1 relative to the GL was associated with an increased risk of PJK after ASD surgery. The postoperative L1-GL distance may be a factor to consider during ASD surgery.
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STUDY DESIGN: Retrospective study. OBJECTIVE: The aim of this study was to investigate whether there is an association between revision surgery rates for adjacent segment degeneration (ASD) and Roussouly type after L4-5 transforaminal lumbar interbody fusion (TLIF) for spondylolisthesis. SUMMARY OF BACKGROUND DATA: Revision surgery for ASD is known to occur after spinal fusion; however, it is unclear whether rates of ASD are associated with certain Roussouly types. METHODS: Patients who underwent L4-5 TLIF for spondylolisthesis at the University of California San Francisco from January 2006 to December 2016 with minimum 2-year follow-up were retrospectively analyzed by Roussouly type. Revision surgery for ASD was noted and correlated by Roussouly type. Spinopelvic parameters were also measured for correlation. A value of Pâ<â0.05 was significant. RESULTS: There were 174 patients who met inclusion criteria, (59 males and 115 females). The average age was 62.3 (25-80) years. A total of 132 patients had grade I spondylolisthesis, and 42 had grade II. Mean follow-up was 45.2âmonths (24-497). A total of 22 patients (12.6%) underwent revision surgery for ASD after L4-5 TLIF. When classified by Roussouly type, revision surgery rates for ASD were: 1, 14.3%; 2, 22.6%; 3, 4.9%; and 4, 15.6% (Pâ=â0.013). Type 3 spines with normal PI-LL (8.85°â±â6.83°) had the lowest revision surgery rate (4.9%), and type 2 spines with PI-LL mismatch (11.06°â±â8.81°) had the highest revision surgery rate (22.6%), a four-fold difference (Pâ=â0.013). The PI-LL mismatch did not change significantly in each type postoperatively (Pâ>â0.05). CONCLUSION: We found that there may be a correlation between Roussouly type and revision surgery for ASD after L4-5 TLIF for spondylolisthesis, with type 2 spines having the highest rate. Spinopelvic parameters may also correlate with revision surgery for ASD after L4-5 TLIF.Level of Evidence: 4.
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Fusão Vertebral , Espondilolistese , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Resultado do TratamentoRESUMO
Metastasis and chemoresistance indicate poor prognosis in patients with osteosarcoma (OS). In the present study, the expression level of microRNA(miR)487b3p in OS specimens and cell lines was found to be decreased, and the expression level of miR487b3p was associated with overall survival in patients with OS. The inhibition of miR487b3p stimulated OS cell migration and contributed to the development of chemoresistance. In contrast, the overexpression of miR487b3p significantly inhibited OS cell migration and enhanced the sensitivity of OS cells to doxorubicin treatment. In addition, the results from the present study revealed that the suppression of miR487b3p stimulates OS stemness, while the overexpression of miR487b3p suppresses OS stemness. Notably, in vivo experiments also revealed that the overexpression of miR487b3p inhibited cancer stem cell (CSC)induced tumor formation, and the combination treatment of miR487b3p and doxorubicin significantly inhibited CSCinduced tumor growth. Furthermore, miR487b3p exerts its anticancer role by targeting aldehyde dehydrogenase 1 family member A3 in OS. Taken together, the results from the present study suggests that miR487b3p is a tumor suppressor and that the overexpression of miR487b3p is a novel strategy to inhibit tumor metastasis and chemoresistance in OS.
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Aldeído Oxirredutases/genética , Neoplasias Ósseas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Osteossarcoma/tratamento farmacológico , Adulto , Idoso , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Biópsia , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Regulação Neoplásica da Expressão Gênica , Voluntários Saudáveis , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Osteossarcoma/genética , Osteossarcoma/mortalidade , Osteossarcoma/secundário , Taxa de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto JovemRESUMO
The posterior column osteotomy (PCO) is a tool for correction in spinal deformity. It allows for the induction of lordosis and coronal plane correction. It can be performed at multiple levels to loosen and mobilize the spine. Although the PCO does not provide as much correction as a 3-column osteotomy, it can be done in less operative time and with less morbidity. Performing a PCO involves the resection of posterior bony elements, including entire facet complexes, the ligamentum flavum, and at least part of the lamina. The ligamentum flavum laterally is also resected, and the exiting nerve roots are skeletonized bilaterally. Compression of the osteotomy can cause foraminal stenosis, and it is important to ensure that the exiting nerve roots are adequately decompressed to avoid potential postoperative radiculopathy. The authors present an illustration of the technique with saw bones, a clinical case describing the use of PCOs, and an intraoperative video of a PCO performed at L5-S1. The patient consented to the surgical procedure and video/image recording for possible publication purposes prior to the operation being performed.
Assuntos
Lordose , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Osteotomia , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to investigate whether fat infiltration of the lumbar multifidus (LM) muscle affects revision surgery rates for adjacent-segment degeneration (ASD) after L4-5 transforaminal lumbar interbody fusion (TLIF) for degenerative spondylolisthesis. METHODS: A total of 178 patients undergoing single-level L4-5 TLIF for spondylolisthesis (2006 to 2016) were retrospectively analyzed. Inclusion criteria were a minimum 2-year follow-up, preoperative MR images and radiographs, and single-level L4-5 TLIF for degenerative spondylolisthesis. Twenty-three patients underwent revision surgery for ASD during the follow-up. Another 23 patients without ASD were matched with the patients with ASD. Demographic data, Roussouly curvature type, and spinopelvic parameter data were collected. The fat infiltration of the LM muscle (L3, L4, and L5) was evaluated on preoperative MRI using the Goutallier classification system. RESULTS: A total of 46 patients were evaluated. There were no differences in age, sex, BMI, or spinopelvic parameters with regard to patients with and those without ASD (p > 0.05). Fat infiltration of the LM was significantly greater in the patients with ASD than in those without ASD (p = 0.029). Fat infiltration was most significant at L3 in patients with ASD than in patients without ASD (p = 0.017). At L4 and L5, there was an increasing trend of fat infiltration in the patients with ASD than in those without ASD, but the difference was not statistically significant (p = 0.354 for L4 and p = 0.077 for L5). CONCLUSIONS: Fat infiltration of the LM may be associated with ASD after L4-5 TLIF for spondylolisthesis. Fat infiltration at L3 may also be associated with ASD at L3-4 after L4-5 TLIF.
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OBJECTIVE: In this study, the authors' aim was to investigate whether obesity affects surgery rates for adjacent-segment degeneration (ASD) after transforaminal lumbar interbody fusion (TLIF) for spondylolisthesis. METHODS: Patients who underwent single-level TLIF for spondylolisthesis at the University of California, San Francisco, from 2006 to 2016 were retrospectively analyzed. Inclusion criteria were a minimum 2-year follow-up, single-level TLIF, and degenerative lumbar spondylolisthesis. Exclusion criteria were trauma, tumor, infection, multilevel fusions, non-TLIF fusions, or less than a 2-year follow-up. Patient demographic data were collected, and an analysis of spinopelvic parameters was performed. The patients were divided into two groups: mismatched, or pelvic incidence (PI) minus lumbar lordosis (LL) ≥ 10°; and balanced, or PI-LL < 10°. Within the two groups, the patients were further classified by BMI (< 30 and ≥ 30 kg/m2). Patients were then evaluated for surgery for ASD, matched by BMI and PI-LL parameters. RESULTS: A total of 190 patients met inclusion criteria (72 males and 118 females, mean age 59.57 ± 12.39 years). The average follow-up was 40.21 ± 20.42 months (range 24-135 months). In total, 24 patients (12.63% of 190) underwent surgery for ASD. Within the entire cohort, 82 patients were in the mismatched group, and 108 patients were in the balanced group. Within the mismatched group, adjacent-segment surgeries occurred at the following rates: BMI < 30 kg/m2, 2.1% (1/48); and BMI ≥ 30 kg/m2, 17.6% (6/34). Significant differences were seen between patients with BMI ≥ 30 and BMI < 30 (p = 0.018). A receiver operating characteristic curve for BMI as a predictor for ASD was established, with an AUC of 0.69 (95% CI 0.49-0.90). The optimal BMI cutoff value determined by the Youden index is 29.95 (sensitivity 0.857; specificity 0.627). However, in the balanced PI-LL group (108/190 patients), there was no difference in surgery rates for ASD among the patients with different BMIs (p > 0.05). CONCLUSIONS: In patients who have a PI-LL mismatch, obesity may be associated with an increased risk of surgery for ASD after TLIF, but in obese patients without PI-LL mismatch, this association was not observed.
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It is morphologically demonstrated that the subfornical organ (SFO) projects to the paraventricular hypothalamic nucleus (PVN) and also projects to the nucleus preopticus medianus (POMe), a relay nucleus of indirect projections from the SFO to PVN. However, it remains unknown, whether or not SFO neurons project collaterally to the POMe and PVN. To confirm this, a double retrograde labeling method was performed on rats using two fluorescent tracers. One tracer (red-colored FluoSpheres: FSR) was injected into the POMe and the other (Fast Blue: FB) was injected into the unilateral PVN at the same time. As a result, many retrogradely labeled neurons were found in the entire SFO. Of these, some neurons showed both FSR and FB fluorescence. Double-labeled neurons were found in about 8.7% of FSR-labeled neurons and 15.5% of FB-labeled neurons. The existence of double-labeled neurons indicates that single neurons in the SFO project simultaneously to the POMe and PVN via collateral axon branches. The data suggest that there are complicated neuronal pathways originating from the SFO in regulating cardiovascular and body fluid homeostasis.
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Núcleo Hipotalâmico Paraventricular/anatomia & histologia , Área Pré-Óptica/anatomia & histologia , Órgão Subfornical/anatomia & histologia , Animais , Axônios/fisiologia , Axônios/ultraestrutura , Mapeamento Encefálico , Fenômenos Fisiológicos Cardiovasculares , Corantes Fluorescentes , Homeostase/fisiologia , Masculino , Microesferas , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
Ovarian cancer G protein-coupled receptor 1 (OGR1) has been shown to be a receptor for protons. We investigated the role of proton-sensing G protein-coupled receptors in the apoptosis of endplate chondrocytes induced by extracellular acid. The expression of proton-sensing G protein-coupled receptors was examined in rat lumbar endplate chondrocytes. Knockdown of OGR1 was achieved by transfecting chondrocytes with specific short hairpin RNA (shRNA) for OGR1. Apoptotic changes were evaluated by DNA fragmentation ELISA, electron microscopy, and flow cytometry. Intracellular calcium ([Ca(2+) ]i) was analyzed with laser scanning confocal microscopy. The mechanism of OGR1 in acid-induced apoptosis of endplate chondrocytes was also investigated. We found that OGR1 was predominantly expressed in rat endplate chondrocytes, and its expression was highly upregulated in response to acidosis. Knocking down OGR1 with shRNAs effectively attenuated acid-induced apoptosis of endplate chondrocytes and increased [Ca(2+) ]i. Blocking OGR1-mediated [Ca(2+) ]i elevation inhibited acid-induced calcium-sensitive proteases such as calpain and calcineurin, and also inhibited the activation of Bid, Bad, and Caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP). OGR1-mediated [Ca(2+) ]i elevation has a crucial role in apoptosis of endplate chondrocytes by regulating activation of calcium-sensitive proteases and their downstream signaling.
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Cálcio/metabolismo , Condrócitos/efeitos dos fármacos , Disco Intervertebral/efeitos dos fármacos , Receptores Acoplados a Proteínas G/fisiologia , Acidose/metabolismo , Animais , Apoptose/efeitos dos fármacos , Calcineurina/biossíntese , Calpaína/biossíntese , Condrócitos/metabolismo , Concentração de Íons de Hidrogênio , Disco Intervertebral/metabolismo , Masculino , Prótons , RNA Interferente Pequeno/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/biossínteseRESUMO
BACKGROUND: Inflammatory cytokines are involved in intervertebral disc (IVD) degeneration. Endothelin-1 (ET-1), a 21-amino-acid cytokine implicated with cartilage degradation, is secreted by vascular endothelial cells and also by many other cell types. The expression of ET-1 in human IVD cartilage endplate (CEP) and its role in disc degeneration have not been explored. METHODS AND FINDINGS: The expression of ET-1 in degenerated CEP was analyzed by immunohistochemical staining and Western blotting; ET-1 was demonstrated in cartilaginous endplate cells (CECs) by immunofluorescent staining. The ET-1 mRNA expression and protein production by CECs stimulated by tumor necrosis factor alpha (TNF-α), a pro-inflammatory cytokine, were determined by real-time PCR analysis and Western blotting, respectively. The matrix metalloprotease-1 (MMP-1), MMP-13 and tissue inhibitor of metalloproteases-1 (TIMP-1) levels in the supernatant of cultured CECs treated with ET-1 were determined using enzyme-linked immunosorbent assays. Nitric oxide (NO) release and nitric oxide synthase (NOS) activity were measured using a spectrophotometric assay. The apoptosis of CECs by ET-1 was measured by an Annexin V-FITC detection assay. The production of ET-1 in degenerated cartilage endplate was significantly higher than normal CEP. The results showed that ET-1 was expressed by CECs and modulated by TNF-α in a dose-dependent manner. ET-1 increased production of MMP-1 and MMP-13, decreased TIMP-1 production, and induced NO and NOS release by cultured CECs. The direct stimulation of CECs by ET-1 did not promote cell apoptosis. CONCLUSION: The study results suggest that ET-1 played a pivotal role in human CEP degeneration, and may be a new target for development of therapies for this condition.
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Cartilagem/metabolismo , Cartilagem/patologia , Endotelina-1/genética , Degeneração do Disco Intervertebral/genética , Adulto , Idoso , Apoptose/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Endotelina-1/metabolismo , Endotelina-1/farmacologia , Feminino , Humanos , Degeneração do Disco Intervertebral/metabolismo , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Pessoa de Meia-Idade , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Adulto JovemRESUMO
PURPOSE: The aim of this study was to investigate the biomechanical stability provided by a novel, polylactic acid/nano-sized, ß-tricalcium phosphate, bioabsorbable, self-retaining cervical fusion cage (BCFC). METHODS: Quasistatic nonconstraining torques (maximum 1.5 NM) induced flexion, extension, lateral bending (±1.5 NM), and axial rotation (±1.5 NM) on 32 sheep cervical spines (C2-C5). The motion segment C3-C4 was first tested intact; the following groups were tested after complete discectomy: autologous tricortical iliac crest bone graft, Medtronic-Wego polyetheretherketone (PEEK) cage, Solis PEEK cage, and BCFC. The autologous bone graft group was tested with an anterior plate. The mean range of motion (ROM) was calculated from the load-displacement curves. RESULTS: BCFC significantly decreased ROM in lateral bending and axial rotation compared to other implants, and no significant difference in ROM between two types of PEEK cages and BCFC could be observed in flexion and extension. Anterior cervical plate (ACP) significantly decreased ROM in flexion and extension, but no significant difference in ROM between BCFC and bone graft plus ACP could be determined in lateral bending and axial rotation. CONCLUSION: The BCFC device showed better stability to autologous tricortical iliac crest bone graft and PEEK cages in single-level anterior cervical discectomy and fusion models and thus may be a potential alternative to the current PEEK cages.
Assuntos
Implantes Absorvíveis , Placas Ósseas , Fosfatos de Cálcio/química , Vértebras Cervicais/cirurgia , Ácido Láctico/química , Nanoestruturas/química , Polímeros/química , Fusão Vertebral/instrumentação , Animais , Terapia Combinada , Discotomia/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Instabilidade Articular , Nanotecnologia/instrumentação , Poliésteres , Ovinos , Resultado do TratamentoRESUMO
The purpose of this study was to investigate the influence of nano-sized ß-tricalcium phosphate (ß-TCP) on the biological performance of poly (lactic acid) (PLA) composite scaffolds by using in vitro degradation and an in vivo model of heterotopic bone formation. Nano-sized ß-TCP (nß-TCP) was prepared with a wet grinding method from micro-sized ß-TCP (mß-TCP), and composite scaffolds containing 0, 10, 30, or 50 wt% nß-TCP or 30 wt% mß-TCP were generated using a freeze-drying method. Degradation was assessed by monitoring changes in microstructure, pH, weight, and compressive strength over a 26-week period of hydrolysis. Composite scaffolds were processed into blocks, and implanted into muscular pockets of rabbits after loading with recombinant human bone morphogenetic protein-2 (rhBMP-2). New bone formation was evaluated based on histological and immunohistochemical analysis 2, 4, and 8 weeks after implantation. The in vitro results indicated that the buffering effect of nß-TCP was stronger than mß-TCP, which was positively correlated with the content of nß-TCP. The in vivo findings demonstrated that nß-TCP enhanced the osteoconductivity of the scaffolds. Although composite scaffolds containing 30% nß-TCP exhibited similar osteoconductivity to 50% nß-TCP, they had better mechanical properties than the 50% nß-TCP scaffolds. This study supports the potential application of a composite scaffold containing 30% nß-TCP as a promising scaffold for bone regeneration.