RESUMO
The amiloride-sensitive epithelial sodium channel (ENaC) is a major contributor to intracellular sodium homeostasis. In addition to epithelial cells, osteoblasts (Obs) express functional ENaCs. Moreover, a correlation between bone Na content and bone disease has been reported, suggesting that ENaC-mediated Na(+) regulation may influence osteogenesis. Obs were isolated and cultured by enzyme digestion. Cell proliferation and differentiation were evaluated by WST-8 assay kit and AKP assay kit respectively. PKGII expression was silenced by siRNA. The mRNA expression was investigated by semi-quantitative PCR and the protein expression was determined by Western-blot. The cell-permeable cGMP analog 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP) increased α-ENaC channel expression in primary rat Obs as indicated by RT-PCR. In addition, 8-pCPT-cGMP stimulation enhanced expression of the mRNA encoding cGMP-dependent protein kinases II (PKGII). The cGMP analog also promoted osteoblast proliferation, differentiation and induced the expression of several osteogenic genes, including core binding factor al, osteocalcin, alkaline phosphatase, collagen type I, and osteopontin. Furthermore, the expression of α-ENaC, the main functional subunit of ENaC, was reduced when a small interfering RNA specific for PKGII was introduced into Obs. Treatment with 8-pCPT-cGMP in cells transfected with the siRNA for PKGII partially reversed downregulated α-ENaC mRNA expression. Our results suggest that 8-pCPT-cGMP stimulates proliferation, differentiation, and osteogenic gene expression in Obs through cGMP/PKGII-dependent regulation of ENaC channel expression. The cGMP/PKGII signaling pathway is a potential target for pharmaceutical interventions to treat metabolic bone diseases.
Assuntos
Proteína Quinase Dependente de GMP Cíclico Tipo II/metabolismo , GMP Cíclico/metabolismo , Canais Epiteliais de Sódio/metabolismo , Osteoblastos/metabolismo , Osteogênese/fisiologia , Transdução de Sinais , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Proteína Quinase Dependente de GMP Cíclico Tipo II/genética , Canais Epiteliais de Sódio/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Knockout , Osteoblastos/citologia , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Ratos , Tionucleotídeos/farmacologiaRESUMO
OBJECTIVE: Spondylotic changes in the cervical spine cause degeneration, leading to cervical spinal canal stenosis. This stenotic change can affect cerebrospinal fluid (CSF) dynamics by compressing the dural sac and reducing space in the subarachnoid space. We examined CSF dynamics at the craniovertebral junction (CVJ) using time-spatial labeling inversion pulse magnetic resonance imaging (Time-SLIP MRI) in patients with cervical spinal canal stenosis. METHODS: The maximum longitudinal movement of the CSF at the CVJ was measured as length of motion (LOM) in the Time-SLIP MRI of 56 patients. The sum of ventral and dorsal LOM was defined as the total LOM. Patients were classified into 3 groups depending on their spinal sagittal magnetic resonance imaging findings: control (n = 27, Kang classification grades 0 and 1), stenosis (n = 14, Kang classification grade 2), and severe stenosis (n = 15, Kang classification grade 3). RESULTS: Time-SLIP MRI revealed pulsatile movement of the CSF at the CVJ. The mean total, ventral, and dorsal LOM was 14.2 ± 9, 8.1 ± 5.7, and 3.8 ± 2.9 mm, respectively. The ventral LOM was significantly larger than the dorsal LOM. The total LOM was significantly smaller in the severe stenosis group (6.1 ± 3.4 mm) than in the control (16.0 ± 8.4 mm) or stenosis (11 ± 5.4 mm) groups (P < 0.001, Kruskal-Wallis H-test). In 5 patients, postoperative total LOM was improved after adequate decompression surgery. CONCLUSIONS: This study demonstrates that CSF dynamics at the CVJ are influenced by cervical spinal canal stenosis. Time-SLIP MRI is useful for evaluating CSF dynamics at the CVJ in patients with spinal canal stenosis.
Assuntos
Imageamento por Ressonância Magnética , Estenose Espinal , Humanos , Constrição Patológica/patologia , Imageamento por Ressonância Magnética/métodos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Estenose Espinal/patologia , Radiografia , Canal Medular/diagnóstico por imagem , Canal Medular/patologia , Vértebras Cervicais/cirurgia , Líquido Cefalorraquidiano/diagnóstico por imagemRESUMO
The Hedgehog pathway functions as an organizer in embryonic development. Aberrant activation of the Hedgehog pathway has been reported in various types of malignant tumours. The GLI2 transcription factor is a key mediator of Hedgehog pathway but its contribution to neoplasia is poorly understood. To establish the role of GLI2 in osteosarcoma, we examined its expression by real-time PCR using biopsy tissues. To examine the function of GLI2, we evaluated the growth of osteosarcoma cells and their cell cycle after GLI2 knockdown. To study the effect of GLI2 activation, we examined mesenchymal stem cell growth and the cell cycle after forced expression of GLI2. We found that GLI2 was aberrantly over-expressed in human osteosarcoma biopsy specimens. GLI2 knockdown by RNA interferences prevented osteosarcoma growth and anchorage-independent growth. Knockdown of GLI2 promoted the arrest of osteosarcoma cells in G(1) phase and was accompanied by reduced protein expression of the cell cycle accelerators cyclin D1, SKP2 and phosphorylated Rb. On the other hand, knockdown of GLI2 increased the expression of p21(cip1) . In addition, over-expression of GLI2 promoted mesenchymal stem cell proliferation and accelerated their cell cycle progression. Finally, evaluation of mouse xenograft models showed that GLI2 knockdown inhibited the growth of osteosarcoma in nude mice. Our findings suggest that inhibition of GLI2 may represent an effective therapeutic approach for patients with osteosarcoma.
Assuntos
Neoplasias Ósseas/metabolismo , Fatores de Transcrição Kruppel-Like/fisiologia , Proteínas Nucleares/fisiologia , Osteossarcoma/metabolismo , Animais , Neoplasias Ósseas/patologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas de Silenciamento de Genes , Proteínas Hedgehog/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/deficiência , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Mesenquimais/patologia , Camundongos , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/fisiologia , Transplante de Neoplasias , Proteínas Nucleares/deficiência , Proteínas Nucleares/metabolismo , Osteossarcoma/patologia , Piridinas/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/fisiologia , Fatores de Transcrição/antagonistas & inibidores , Transplante Heterólogo , Células Tumorais Cultivadas , Proteína GLI1 em Dedos de Zinco , Proteína Gli2 com Dedos de ZincoRESUMO
STUDY DESIGN: A prospective study. OBJECTIVES: To assess the outcome of patients with a single thoracolumbar burst fracture treated with circumferential short-segment fusion consisting of posterior reduction, short-segment fusion, and delayed staged mini-open anterior short-segment fusion. SUMMARY OF BACKGROUND DATA: The surgical treatment of thoracolumbar burst fractures remains controversial. In attempting to combine the advantages of posterior procedures, including initial correction of kyphosis and early decompression, and those of anterior procedures, including direct decompression and restoration of anterior column support, a combined posterior and delayed staged anterior procedure seems to be a reasonable choice. However, conventional combined procedures are invasive. METHODS: We prospectively selected 28 consecutive patients with single thoracolumbar burst fracture for circumferential short-segment fusion consisting of posterior reduction, short-segment fusion, and delayed staged mini-open anterior short-segment fusion. The pedicle screw systems were removed after confirmation of posterior bony fusion to preserve as many motion segments as possible in those patients who could be treated with circumferential monosegmental fusion. Radiographic and clinical assessment of 28 patients who received this treatment was carried out. RESULTS: The mean loss of correction of kyphosis between the time of the combined procedure and final follow-up was 3.7 degrees (range, 0 to 10.2 degrees). Bony fusion was eventually achieved in all patients. There were 15 cases with monosegmental and 13 cases with bisegmental circumferential fusion. All 10 patients with initial neurological deficit improved by at least 1 Frankel grade: 3 improved by 1 grade, 5 improved by 2 grades, and 2 improved by 3 grades. In total, 27 patients, who were P1 or P2 on the Denis pain scale, were considered to have obtained clinically satisfactory results. CONCLUSIONS: This combined procedure is less invasive than the conventional combined one, and finally achieves shorter stabilization, resulting in preservation of motion segments. It thus seems to be a reasonable treatment option for thoracolumbar burst fractures.
Assuntos
Vértebras Lombares/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Adolescente , Adulto , Idoso , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
GADD45beta (growth arrest- and DNA damage-inducible) interacts with upstream regulators of the JNK and p38 stress response kinases. Previously, we reported that the hypertrophic zone of the Gadd45beta(-/-) mouse embryonic growth plate is compressed, and expression of type X collagen (Col10a1) and matrix metalloproteinase 13 (Mmp13) genes is decreased. Herein, we report that GADD45beta enhances activity of the proximal Col10a1 promoter, which contains evolutionarily conserved AP-1, cAMP-response element, and C/EBP half-sites, in synergism with C/EBP family members, whereas the MMP13 promoter responds to GADD45beta together with AP-1, ATF, or C/EBP family members. C/EBPbeta expression also predominantly co-localizes with GADD45beta in the embryonic growth plate. Moreover, GADD45beta enhances C/EBPbeta activation via MTK1, MKK3, and MKK6, and dominant-negative p38alphaapf, but not JNKapf, disrupts the combined trans-activating effect of GADD45beta and C/EBPbeta on the Col10a1 promoter. Importantly, GADD45beta knockdown prevents p38 phosphorylation while decreasing Col10a1 mRNA levels but does not affect C/EBPbeta binding to the Col10a1 promoter in vivo, indicating that GADD45beta influences the transactivation function of DNA-bound C/EBPbeta. In support of this conclusion, we show that the evolutionarily conserved TAD4 domain of C/EBPbeta is the target of the GADD45beta-dependent signaling. Collectively, we have uncovered a novel molecular mechanism linking GADD45beta via the MTK1/MKK3/6/p38 axis to C/EBPbeta-TAD4 activation of Col10a1 transcription in terminally differentiating chondrocytes.
Assuntos
Antígenos de Diferenciação/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Condrócitos/citologia , Condrócitos/fisiologia , Colágeno Tipo X/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Fator 1 Ativador da Transcrição/metabolismo , Animais , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Lâmina de Crescimento/citologia , Lâmina de Crescimento/embriologia , Lâmina de Crescimento/fisiologia , Humanos , MAP Quinase Quinase 3/metabolismo , MAP Quinase Quinase 6/metabolismo , MAP Quinase Quinase Quinase 1/metabolismo , MAP Quinase Quinase Quinase 4/metabolismo , Metaloproteinase 13 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/fisiologia , Teratocarcinoma , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Most spinal meningiomas arise from the thoracic dura in middle-aged and elderly women. Simpson grade 1 resection is recommended to avoid recurrence. For ventral and ventrolateral tumors, reconstruction after total dural resection is difficult, and spinal fluid leakage is likely. To overcome this concern, Saito et al. developed the technique of resecting the tumor with the inner dural layer, preserving the outer dural layer. Although meningioma rarely recurs, the recurrence period is approximately 8 years postoperatively. No studies have evaluated long-term (> 10-year) outcomes of the Saito method. Here, we report 10 cases of the Saito method with > 10-year follow-up and compare outcomes with those of other standard approaches. Twenty-nine pathology-confirmed meningioma patients underwent surgery in our department, ten with the Saito method. We investigated resection method (dura mater treatment), pathological type, and recurrence and compared pre- and postoperative clinical findings. The median follow-up was 132 months. Recurrence occurred after Simpson grades 3 and 4 resection. Simpson grades 1, 2, and the Saito method resulted in no recurrence. Neurological symptoms improved in all patients at final follow-up. This is the first report of long-term outcomes of the Saito method. The method achieved good neurological improvement with no recurrence in > 10-year follow-up.
Assuntos
Dura-Máter/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Idoso , Dura-Máter/patologia , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologiaRESUMO
Spinal subependymomas, which have a relatively benign nature, are very rare tumors. It is difficult to distinguish spinal subependymomas from other intramedullary spinal tumors based on neuroradiological findings. A case of cervical intramedullary subependymoma in a 63-year-old female is reported. The diffused enlargement of the spinal cord at C2 level involved the lesion with isointensity on a T1-weighted MRI and relatively high intensity on a T2-weighted MRI. Enhancement in the small part of the tumor was observed on a T1-weighted MRI with gadolinium administration. The tumor occupied the left side of the spinal cord, and was totally removed through a laminoplasty of C2. Immunohistochemistry was useful for pathological diagnosis. The clinical feature of this patient is described with the review of literatures.
Assuntos
Epêndima/patologia , Glioma Subependimal/patologia , Neoplasias da Medula Espinal/patologia , Medula Espinal/patologia , Epêndima/química , Epêndima/cirurgia , Feminino , Glioma Subependimal/química , Glioma Subependimal/cirurgia , Humanos , Pessoa de Meia-Idade , Medula Espinal/química , Medula Espinal/cirurgia , Neoplasias da Medula Espinal/química , Neoplasias da Medula Espinal/cirurgiaRESUMO
Tethered cord syndrome with spinal lipoma is the most common form of occult spinal dysraphism. For the symptomatic patients, surgical treatment is recommended; however, there are many patients who have not been encouraged to seek medical attention until adulthood, since their symptoms are not severe enough to interfere with their daily activities. We performed pedicle subtraction osteotomy (PSO) to achieve indirect untethering and neural decompression in two senior patients with tethered cord syndrome, who showed deteriorating neurological condition due to coexisting lumbar canal stenosis. Here we report two patients (aged 56 and 60 years) who underwent PSO of L3 or L4. The pain disappeared and the bladder dysfunction recovered significantly after surgery. Complete bone union and untethering were achieved in both patients. PSO is an alternative surgical technique for senior patients with tethered cord syndrome caused by lumbosacral spinal lipoma, when the syndrome occurs along with lumbar canal stenosis.
Assuntos
Dor Lombar/etiologia , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/cirurgia , Bexiga Urinaria Neurogênica/etiologia , Idoso , Transtornos Neurológicos da Marcha , Humanos , Laminectomia , Lipoma/patologia , Lipoma/cirurgia , Lordose/patologia , Lordose/cirurgia , Dor Lombar/fisiopatologia , Dor Lombar/cirurgia , Vértebras Lombares/patologia , Região Lombossacral/patologia , Masculino , Pessoa de Meia-Idade , Osteotomia , Fusão Vertebral , Coluna Vertebral/patologia , Coluna Vertebral/cirurgia , Resultado do Tratamento , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinaria Neurogênica/cirurgiaRESUMO
Intradural neurenteric cysts are rare congenital lesions and arise from incomplete separation of the developing notochord and foregut in the embryo. Neurenteric cysts are often seen in conjunction with other forms of occult spinal dysraphism. The cases of a 48-year-old male with pain in the right shoulder and numbness in both hands and a 7-year-old girl with subacute muscle weakness of the lower extremities are presented. Both patients underwent surgery. One lesion was completely excised, while the other could be only partially removed because of negative monitoring potential during the operation. Histological examination, showing pseudostratified ciliated columnar epithelium, confirmed the diagnosis of neurenteric cyst. The symptoms in both patients nearly disappeared after surgery. Recurrence of cyst was observed in the girl, though without neurological symptoms. In conclusion, two cases of intradural extramedullary cysts are reported. Clinical presentations, intraoperative findings, and histological features are discussed with a review of the literature.
Assuntos
Defeitos do Tubo Neural/cirurgia , Doenças da Medula Espinal/cirurgia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Defeitos do Tubo Neural/embriologia , Defeitos do Tubo Neural/patologia , Doenças da Medula Espinal/embriologiaRESUMO
Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. MK acts as a reparative neurotrophic factor in damaged peripheral nerves. A postulated role of MK in the degeneration and regeneration of sciatic nerves was explored by comparing wild-type (Mdk(+/+)) mice with MK-deficient (Mdk(-/-)) mice after freezing injury. In the Mdk(-/-) mice, a regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). The relative wet weight of the soleus muscle slowly declined, and recovery was delayed compared with that in the Mdk(+/+) mice. In the regenerating nerve, unmyelinated axons were unevenly distributed, and some axons contained myelin-like, concentrically lamellated bodies. In the endplates of soleus muscles, nerve terminals containing synaptic vesicles disappeared in both mice. In Mdk(-/-) mice, the appearance of nerve terminals was delayed in synaptic vesicles of terminal buttons after injury. The recovery of evoked electromyogram was delayed in Mdk(-/-) mice compared with Mdk(+/+) mice. Our results suggested a delay in axonal degeneration and regeneration in Mdk(-/-) mice compared with Mdk(+/+) mice, and the delayed regeneration was associated with a delayed recovery of motor function. These findings show that a lack of MK following peripheral nerve injury is a critical factor in degeneration and regeneration, and manipulation of the supply of MK may offer interesting therapeutic options for the treatment of peripheral nerve damage.
Assuntos
Citocinas/fisiologia , Regeneração Nervosa/fisiologia , Nervo Isquiático/lesões , Degeneração Walleriana/fisiopatologia , Animais , Citocinas/deficiência , Citocinas/genética , Eletromiografia , Congelamento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Midkina , Placa Motora/ultraestrutura , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Fibras Nervosas Amielínicas/patologia , Regeneração Nervosa/genética , Recuperação de Função Fisiológica , Nervo Isquiático/metabolismo , Degeneração Walleriana/genéticaRESUMO
The epithelium-specific ETS (ESE)-1 transcription factor is induced in chondrocytes by interleukin-1beta (IL-1beta). We reported previously that early activation of EGR-1 by IL-1beta results in suppression of the proximal COL2A1 promoter activity by displacement of Sp1 from GC boxes. Here we report that ESE-1 is a potent transcriptional suppressor of COL2A1 promoter activity in chondrocytes and accounts for the sustained, NF-kappaB-dependent inhibition by IL-1beta. Of the ETS factors tested, this response was specific to ESE-1, since ESE-3, which was also induced by IL-1beta, suppressed COL2A1 promoter activity only weakly. In contrast, overexpression of ETS-1 increased COL2A1 promoter activity and blocked the inhibition by IL-1beta. These responses to ESE-1 and ETS-1 were confirmed using siRNA-ESE1 and siRNA-ETS1. In transient cotransfections, the inhibitory responses to ESE-1 and IL-1beta colocalized in the -577/-132 bp promoter region, ESE-1 bound specifically to tandem ETS sites at -403/-381 bp, and IL-1-induced binding of ESE-1 to the COL2A1 promoter was confirmed in vivo by ChIP. Our results indicate that ESE-1 serves a potent repressor function by interacting with at least two sites in the COL2A1 promoter. However, the endogenous response may depend upon the balance of other ETS factors such as ETS-1, and other IL-1-induced factors, including EGR-1 at any given time. Intracellular ESE-1 staining in chondrocytes in cartilage from patients with osteoarthritis (OA), but not in normal cartilage, further suggests a fundamental role for ESE-1 in cartilage degeneration and suppression of repair.
Assuntos
Condrócitos/metabolismo , Colágeno Tipo II/genética , Proteínas de Ligação a DNA/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Fatores de Transcrição/fisiologia , Transcrição Gênica/fisiologia , Cartilagem/metabolismo , Células Cultivadas , Cromatina/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Imuno-Histoquímica , Imunoprecipitação , Interleucina-1beta/farmacologia , NF-kappa B/metabolismo , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteína Proto-Oncogênica c-ets-1/genética , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-ets , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Distribuição Tecidual , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia , Transfecção , Regulação para CimaRESUMO
Chordoma arising from the cervical spine is rare and the traditional long-term prognosis is typically poor. Total en bloc spondylectomy with a wide margin is generally accepted to be the most appropriate management for thoracic and lumbar malignant tumors. However, this method is still challenging for the cervical spine because of the proximity of the tumor to the vertebral arteries and neural elements. Here, we report a 73-year-old man with a C5 vertebral chordoma treated with total piecemeal spondylectomy. Histological examination revealed pathognomonic physaliphorous cells with mucus-filled cytoplasm in the tumor, and the ratio of Ki-67-positive cells within the tumor was high (19.0%), showing active proliferation rate. Local recurrences were found at 9 months, 4 years and 2 months, and 6 years after the initial surgery. All the recurrences were encapsulated and isolated and treated with an additional en bloc resection successfully at each stage. Eight years after the initial total piecemeal spondylectomy, the patient maintained his intact neurological status without local recurrence or metastasis. The prognosis of cervical chordoma depends on the patient's age, surgical procedures, and histological features. In this report, we present that piecemeal spondylectomy is an alternative management for aged patients with cervical chordoma, even for those with high MIB-1 index.
RESUMO
Midkine (MK) is a multifunctional cytokine and heparin-binding growth factor with neurotrophic activity. MK and its receptor were examined for up to 14 days in a chemically injured rat muscle regeneration process caused by the injection of bupivacaine using immunohistochemical and Western blot analysis. Although MK immunoreactivity was not detectable in the mature uninjured skeletal muscle, MK was strongly detected in the regenerating muscle cells. MK immunoreactivity was observed in the myoblast-like cells and myotubes, which were desmin-positive cells, whereas it was not detectable in the surviving normal muscle fibers. Most myotubes labeling for desmin showed MK immunoreactivity 5-7days after the injury. However, MK immunoreactivity was not detected 14 days after the injury. Immunoreactivity of low-density lipoprotein receptor-related protein (LRP), a cell membrane receptor of MK, was detected in the regenerating muscle cells, whereas it was not detected in the normal adult skeletal muscle and surviving muscle. These findings suggested that MK was involved. MK may have a role for differentiation during skeletal muscle regeneration and may be taken up in an autocrine fashion with LRP.
Assuntos
Bupivacaína/administração & dosagem , Bupivacaína/farmacologia , Citocinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Receptores de Fatores de Crescimento/metabolismo , Regeneração , Animais , Citocinas/imunologia , Imuno-Histoquímica , Injeções Intraperitoneais , Masculino , Midkina , Músculo Esquelético/citologia , Ratos , Ratos WistarRESUMO
Osteoarthritis (OA) is a whole joint disease characterized by cartilage degradation, which causes pain and disability in older adults. Our previous work showed that growth arrest and DNA damage-inducible protein 45 ß (GADD45ß) is upregulated in chondrocyte clusters in OA cartilage, especially in the early stage of this disease. CCAAT/enhancer binding protein ß (C/EBPß) is expressed in the hypertrophic growth plate chondrocytes and functions in synergy with GADD45ß. Here, the presence and localization of these proteins was assessed by immunohistochemistry using articular cartilage from OA patients, revealing colocalization of C/EBPß and GADD45ß in OA chondrocytes. GADD45ß promoter analysis was performed to determine whether C/EBPß directly regulates GADD45ß transcription. Furthermore, we analyzed the effect of C/EBPß on Gadd45ß gene regulation in articular chondrocytes in vivo and in vitro. Immunohistochemical analysis of C/ebpß-haploinsufficient mice (C/ebpß(+/-)) cartilage showed that C/ebpß haploinsufficiency led to reduced Gadd45ß gene expression in these cells. In vitro, we evaluated the effects of conditional C/EBPß overexpression driven by the cartilage oligomeric matrix protein (Comp) promoter in mComp-tTA;pTRE-Tight-BI-DsRed-mC/ebpß transgenic mice. C/EBPß overexpression significantly stimulated Gadd45ß gene expression in articular chondrocytes. Taken together, our data demonstrate that C/EBPß plays a central role in controlling Gadd45ß gene expression in these cells.
Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteínas de Ciclo Celular/biossíntese , Condrócitos/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteínas Nucleares/biossíntese , Osteoartrite/metabolismo , Idoso , Animais , Western Blotting , Proteína beta Intensificadora de Ligação a CCAAT/genética , Cartilagem Articular/metabolismo , Proteínas de Ciclo Celular/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Osteoartrite/genética , Reação em Cadeia da Polimerase em Tempo Real , Transcrição GênicaRESUMO
INTRODUCTION: Retro-odontoid mass rarely occur in patients with noninflammatory retro-odontoid lesions without atlantoaxial instability. We describe a rare case of retro-odontoid mass without atlantoaxial instability operated on by a transdural approach. CASE PRESENTATION: The patient was an 83-year-old man who presented with a retro-odontoid mass causing symptomatic cervical myelopathy. Preoperative magnetic resonance imaging (MRI) revealed that the mass was severely compressing the spinal cord. We operated on it via a C1 laminectomy and performed tumor resection by a transdural approach. Pathological findings from the operative specimen confirmed the diagnosis; histopathological examination revealed that the mass contained fibrinoid material, and collagenous tissue with myxoid changes, but no granulation or a granulomatous lesion. Postoperative MRI confirmed spinal cord decompression. The patient's symptoms were alleviated, and he has not had a recurrence or cervical instability in the 7 years since his surgery. DISCUSSION: We successfully used a transdural approach in the present case and have observed no recurrence for 7 years postoperatively. C1 laminectomy is reportedly beneficial, especially for elderly patients, given the risk of other surgical options using an anterior transoral approach or posterior fusion. However, most tumors do not attenuate after C1 laminectomy alone; hence, we think that tumor resection by the transdural approach is one effective method to perform enucleation of the tumor after C1 laminectomy.
RESUMO
Spinal cord injury is a debilitating condition. Midkine (MK) is involved in the generation of the central nervous system during development; however, the role of MK in the mature spinal cord has not been clarified. We examined the expression of MK, which has neurotrophic activity, before and after traumatic injury to the adult rat spinal cord. Following laminectomy, the rat spinal cord was injured at the T-9 level by applying extradural static weight-compression, in which a cylindrical compressor was used to induce complete and irreversible transverse spinal cord injury with paralysis of the lower extremities. The expression of MK was examined up to 14 days after the injury by immunohistochemical and Western blot analyses. Intense MK immunoreactivity was observed in the gray matter around the injury site but not in the necrotic lesion 1-7 days postinjury, although it was slightly positive 14 days after the injury. MK immunoreactivity was not detected in the normal spinal cord. The expression of MK was an early event, and its expression was compared to the increased production of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, that was elevated at 2 days postinjury and continued over a 14 day period following the injury. Double immunostaining with anti-MK and anti-GFAP showed the existence of MK in the astrocytic cytoplasm. These findings suggest that MK was produced in astrocytes approximating the damaged region and may represent a reparative neurotrophic factor during the early phase of traumatic injury of the spinal cord.
Assuntos
Proteínas de Transporte/metabolismo , Citocinas , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/crescimento & desenvolvimento , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/metabolismo , Gliose/fisiopatologia , Masculino , Midkina , Fatores de Crescimento Neural/metabolismo , Ratos , Ratos Wistar , Tempo de Reação/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/terapiaRESUMO
Most patients with thoracic ossification of the posterior longitudinal ligament (OPLL) exhibit delayed recovery of gait dysfunction after spinal injury. The hybrid assistive limb (HAL) is a new robot suit controlling knee and hip joint motion by detecting very weak bioelectric signals on the surface of the skin. This study is to report the feasibility and benefits of patient-assistive HAL walking rehabilitation for facilitating locomotor function after spinal surgery. The patient was a 60-year-old woman with thoracic OPLL, and her motor and sensory paralyses did not improve after spinal surgery, indicating severe impairment in the paretic legs. The subject underwent 6 HAL sessions per week for 8 weeks, consisting of a standing and sitting exercise and walking on the ground with HAL. Clinical outcomes were evaluated before and after HAL training and 1 year after surgery. The subject improved considerably as a result of HAL training. Subsequently, her walking ability recovered rapidly, and she was able to walk unaided six months after surgery. This case study suggests that HAL training is a feasible and effective option to facilitating locomotor function and the early HAL training with physiotherapy may enhance motor recovery of patients with residual paralysis after surgery.
RESUMO
Paget disease of bone (PDB) is a bone metabolic disorder causing pain, fractures, and deformity. Its incidence is estimated to be 1 to 2% in Caucasians older than 55 years, but in Asian populations the incidence is rare. We report on 2 female and one male Japanese patients aged 46 to 73 years with PDB. One patient had monostotic disease with pain around the shoulder and the other 2 were asymptomatic. All patients had elevated alkaline phosphatase (ALP) levels (range, 629-957 U/L). Two patients responded to oral bisphosphonate treatment and achieved normalised ALP levels and pain relief. One patient with polyostotic disease did not show any change in ALP levels. The diagnosis of the disease and the indications for bisphosphonate treatment are discussed.
Assuntos
Difosfonatos/uso terapêutico , Osteíte Deformante/diagnóstico , Idoso , Biópsia , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
We report a case of a 69-year-old man with dropped head syndrome associated with isolated neck extensor myopathy (INEM). Over a period of 2 years, he exhibited progressive inability to lift his chin off his chest, resulting in the dropped head position that impaired his activities of daily living. He had a disturbed gait with severe imbalance of spinal alignment. Computed tomography revealed osseous contracture of cervical vertebral bodies in flexed position. Anterior combined posterior reconstruction surgery yielded a successful outcome in his activities of daily living, including his walking balance of spinal alignment. Pathologic study confirmed myogenic atrophy in the cervical extensor muscles. We suggest that consideration for surgical management should be given to dropped head syndrome especially due to INEM.
Assuntos
Transtornos dos Movimentos/etiologia , Debilidade Muscular/etiologia , Doenças Musculares/etiologia , Músculos do Pescoço/patologia , Idoso , Atrofia/complicações , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Humanos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Masculino , Transtornos dos Movimentos/diagnóstico , Transtornos dos Movimentos/cirurgia , Debilidade Muscular/diagnóstico , Debilidade Muscular/cirurgia , Doenças Musculares/diagnóstico , Doenças Musculares/cirurgia , Procedimentos Ortopédicos , Síndrome , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Osteoid osteoma of the spine is a relatively rare bone-forming tumor. Pain that is worse at night and relieved by aspirin and muscle contracture are the most characteristic symptoms of spinal osteoid osteoma. Although radicular pain occasionally occurs in spinal osteoid osteoma, spinal cord and nerve root compression is absent in most cases. Although radicular pain appears to be associated with tumorous inflammation, there have been no presentations of histological findings of inflammation around the nerve root. We present here two rare cases of spinal osteoid osteoma causing radiculopathy and the first histological evidence of tumorous inflammation as a cause of radiculopathy in osteoid osteoma near the intervertebral foramen.