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1.
Tissue Eng Part C Methods ; 26(3): 170-179, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32186996

RESUMO

Cell sheet engineering has become important in a variety of fields, including regenerative medicine and transplantation. Our research group previously developed micromesh cultures that enable cells to form a cell sheet on a microstructured mesh sheet. Here, we present a more usable micromesh culture and devices that make it possible, aiming for widespread use. The devices are mainly constituted of a polyester micromesh sheet and three-dimensional (3D)-printed simple frames that fix the mesh sheet on it. Cells such as fibroblast Tig-1-20 cells, hepatoma HepG2 cells, or mesenchymal stem cells (MSC) were easily seeded on the polyester mesh sheet in the device and cultured for 16 days, which was followed by the formation of a 100-400-µm-thick cell sheet. The cell sheet was very robust, easy to handle, and could be readily removed from the device for subsequent analysis. Optical coherence tomography revealed the structure of the cell sheet as having the mesh sheet layer in the center of the cell sheet. Confocal microscopy demonstrated that Tig-1-20 cells in the cell sheet were aligned according to the shape of the mesh apertures, indicating that cell orientation can be controlled with this micromesh culture. As for another application, the device was used to construct a multilayered cell sheet that consists of three different types of cells. Furthermore, for mass production, the device frames were made using polyoxymethylene (POM) instead of 3D printing materials. Using the POM devices, a large MSC sheet for 10 cm dishes was successfully produced 7 days after cell seeding. This micromesh culture may become one of the useful cell sheet construction methods in future for medical and research fields. Impact statement Currently, cell sheets are constructed, for example, on a temperature-responsive polymer-coated dish or a porous membrane. These cell sheets are widely used but are not completely suitable in terms of robustness, ease of handling, cost, ease of microscopic cell observation, or nutrient supply. We previously reported that the micromesh culture can provide a three-dimensional (3D) cell sheet that has advantages for cell observation and nutrient supply. In this study, the micromesh culture was enhanced with a polyester micromesh sheet and a series of devices of polyoxymethylene, helping us to produce a robust, cost-effective, easily layered, and easy-to-use 3D cell sheet.

2.
J Sports Med Phys Fitness ; 59(10): 1601-1607, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694361

RESUMO

BACKGROUND: Outdoor exercise often proceeds in rainy conditions. However, there are very few studies reporting the physiological effects of cold with rain or wet-cold exposure on humans during exercise. The purpose of this study was to investigate the effects of rain on physiological responses during running exercise at 80% V̇Omax in the cold. METHODS: Twelve healthy men (age: 21.7±3.3 years; height: 1.760±0.085 m; body weight: 68.8±7.1 kg; maximal oxygen consumption: 67.3±5.00 mL/kg/min) exercised on a treadmill at 80% V̇Omax intensity for 60 minutes with rain (RAIN) or not (CON) at 5 °C. RESULTS: Rectal temperature was significantly lower in RAIN than in CON at 10, 40, 50, and 60 minutes (P<0.05). Mean weighted skin temperature was significantly lower in RAIN than in CON during exercise (P<0.05). Oxygen consumption and rating of perceived exertion were significantly higher in RAIN than in CON at 50 and 60 minutes (P<0.05). Plasma lactate was significantly higher in RAIN than in CON at 10 minutes and from 40 to 60 minutes (P<0.05). Plasma norepinephrine levels were significantly higher in RAIN than in CON at 10 minutes and from 40 to 60 minutes (P<0.05). CONCLUSIONS: These results suggest that rain increased heat loss during the early phase of exercise in the cold, then heat production increased and transiently suppressed cold stress. However, with time, body heat loss intensified due to increasing wet area, and then energy expenditure and plasma lactate increased due to cold stress. Therefore, rain may decrease exercise performance and affect sport safety.


Assuntos
Temperatura Baixa/efeitos adversos , Metabolismo Energético/fisiologia , Chuva , Corrida/fisiologia , Adolescente , Adulto , Regulação da Temperatura Corporal/fisiologia , Estudos de Casos e Controles , Teste de Esforço/métodos , Humanos , Ácido Láctico/sangue , Masculino , Consumo de Oxigênio/fisiologia , Temperatura Cutânea , Adulto Jovem
3.
Asian J Neurosurg ; 12(4): 644-647, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29114276

RESUMO

Objective and Background: Surgery of unruptured aneurysms is always a great challenge to neurovascular surgeons because no postoperative neurological deficits should be expected postoperatively as the patients are fully asymptomatic before the surgery. Here, we present our experience with selective motor evoked potential (MEP) monitoring of our patients in a 2-year time window. Patients and Methods: From 2012 to 2014, 27 patients with unruptured intracranial aneurysms were operated in our institute with the help of MEP monitoring. All patients underwent endoscope-assisted microsurgery with pre- and post-clipping indocyanine green angiography. Results: In this period, no mortality was observed, but 18.5% of the patients developed postoperative deficits which showed good recovery in all cases. Overall, MEP showed about 90% accuracy in predicting postoperative deficits. Conclusions: MEP as a part of multimodality monitoring of aneurysm surgeries is a valuable tool to improve the outcome. However, we should know its limitations as its results are not always consistent with the outcome.

4.
No Shinkei Geka ; 45(5): 409-415, 2017 May.
Artigo em Japonês | MEDLINE | ID: mdl-28490683

RESUMO

We report a case of concomitant carotid endarterectomy(CEA)and aortic valve replacement(AVR)for symptomatic severe carotid artery and aortic valve stenosis(AS). A 77-year-old man, presented to our hospital with AS complicated by right internal carotid artery(ICA)stenosis and left ICA occlusion, seeking treatment for AS. He suffered from left hemiparesis, and diffusion-weighted magnetic resonance imaging(MRI)showed multiple ischemic lesions in the right cerebral hemisphere. He was admitted to our neurosurgical department and received treatment for acute cerebral infarction caused by severe right ICA stenosis. The symptomatic severe right ICA stenosis was an indication for surgical treatment, but simple carotid revascularization of the stenosed ICA was considered to be deteriorated the cardiac function due to untreated AS. Thus, we decided to perform concomitant carotid and valvular surgery. The patient underwent a combined CEA and AVR procedure with the introduction of an intraoperative intra-aortic balloon pump. His postoperative course was uneventful even 12 months after the surgery. Management and surgical strategies for patients with concomitant ICA stenosis and AS continue to be controversial subjects. Combined carotid and cardiac valve surgery is considered to be effective in such cases, and we discuss its implications and review of literature.


Assuntos
Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/cirurgia , Estenose das Carótidas/complicações , Estenose das Carótidas/cirurgia , Idoso , Estenose da Valva Aórtica/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Imagem por Ressonância Magnética , Masculino , Resultado do Tratamento
5.
Neurosci Res ; 123: 27-35, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28450152

RESUMO

The open field test is one of the most popular ethological tests to assess anxiety-like behavior in rodents. In the present study, we examined the effect of early deprivation (ED), a model of early life stress, on anxiety-like behavior in rats. In ED animals, we failed to find significant changes in the time spent in the center or thigmotaxis area of the open field, the common indexes of anxiety-like behavior. However, we found a significant increase in high-leaning behavior in which animals lean against the wall standing on their hindlimbs while touching the wall with their forepaws at a high position. The high-leaning behavior was decreased by treatment with an anxiolytic, diazepam, and it was increased under intense illumination as observed in the center activity. In addition, we compared the high-leaning behavior and center activity under various illumination intensities and found that the high-leaning behavior is more sensitive to illumination intensity than the center activity in the particular illumination range. These results suggest that the high-leaning behavior is a novel anxiety-like behavior in the open field test that can complement the center activity to assess the anxiety state of rats.


Assuntos
Ansiedade/etiologia , Comportamento Exploratório/fisiologia , Aprendizagem/fisiologia , Estresse Psicológico/complicações , Animais , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Diazepam/uso terapêutico , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Feminino , Masculino , Atividade Motora/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas
6.
J Orthop Res ; 35(11): 2465-2475, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28303595

RESUMO

Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes. To achieve controlled intra-articular administration of statin, we developed an intra-articular injectable statin using poly(lactic-co-glycolic acid) (PLGA) as a drug delivery system (DDS). The release profile of the statin was evaluated in vitro. Finally, therapeutic effects of fluvastatin-loaded PLGA microspheres (FLU-PLGA) were tested in a rabbit OA model. Rabbit knees were divided into four subgroups: group 1-A, PLGA-treated group; group 1-B, PLGA contralateral saline control group; group 2-A, FLU-PLGA-treated group; and group 2-B, FLU-PLGA contralateral saline control group. Histological analysis 5 weeks after intra-articular injection revealed that OARSI scores were lower in group 2-A. No significant differences in OARSI scores were observed between groups 1-A, 1-B, and 2-B. This study indicates that a single intra-articular injection of fluvastatin-loaded PLGA microspheres could be a novel therapeutic approach for treating patients with OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2465-2475, 2017.


Assuntos
Anticolesterolemiantes/administração & dosagem , Artrite Experimental/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/administração & dosagem , Indóis/administração & dosagem , Osteoartrite/tratamento farmacológico , Animais , Condrócitos/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Fluvastatina , Humanos , Injeções Intra-Articulares , Ácido Láctico , Microesferas , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Cultura Primária de Células , Coelhos
7.
Am J Pathol ; 187(3): 639-653, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28082119

RESUMO

Scar formation is a prominent pathological feature of traumatic central nervous system (CNS) injury, which has long been implicated as a major impediment to the CNS regeneration. However, the factors affecting such scar formation remain to be elucidated. We herein demonstrate that the extracellular matrix protein periostin (POSTN) is a key player in scar formation after traumatic spinal cord injury (SCI). Using high-throughput RNA sequencing data sets, we found that the genes involved in the extracellular region, such as POSTN, were significantly expressed in the injured spinal cord. The expression of POSTN peaked at 7 days after SCI, predominantly in the scar-forming pericytes. Notably, we found that genetic deletion of POSTN in mice reduced scar formation at the lesion site by suppressing the proliferation of the pericytes. Conversely, we found that recombinant POSTN promoted the migration capacity of the monocytes/macrophages and increased the expression of tumor necrosis factor-α from the monocytes/macrophages in vitro, which facilitated the proliferation of pericytes. Furthermore, we revealed that the pharmacological blockade of POSTN suppressed scar formation and improved the long-term functional outcome after SCI. Our findings suggest a potential mechanism whereby POSTN regulates the scar formation after SCI and provide significant evidence that POSTN is a promising therapeutic target for CNS injury.


Assuntos
Moléculas de Adesão Celular/metabolismo , Cicatriz/patologia , Macrófagos/patologia , Monócitos/patologia , Pericitos/patologia , Traumatismos da Medula Espinal/patologia , Animais , Anticorpos Neutralizantes/farmacologia , Axônios/efeitos dos fármacos , Axônios/metabolismo , Axônios/patologia , Moléculas de Adesão Celular/deficiência , Moléculas de Adesão Celular/genética , Proliferação de Células/efeitos dos fármacos , Feminino , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Pericitos/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Fator de Necrose Tumoral alfa/farmacologia
8.
Neuroradiol J ; 30(1): 99-103, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27903923

RESUMO

Posterior cerebral artery (PCA) aneurysms are rare, and direct surgery of these is considered difficult. Coil embolization of PCA aneurysms is becoming popular. However, it is difficult to completely obliterate the aneurysm while preserving the flow of the parent artery in large or giant PCA aneurysms with a wide neck with this technique. We report a case of a large and wide-necked PCA aneurysm with multiple recurrences following successful surgical clipping and coil embolization. A 77-year-old man with a large unruptured right PCA (P2) aneurysm was successfully treated by surgical clipping. Postoperative digital subtraction angiography (DSA) showed complete aneurismal occlusion. Four years afterward, the aneurysm recurred and grew toward the contralateral. Surgical retreatment of this complicated aneurysm was considered difficult, with a substantial risk of complications. Therefore, the aneurysm was treated with an endovascular procedure. Because simple coil embolization was not expected to achieve satisfactory obliteration of the aneurysm with preservation of parent artery patency, we used stent-assisted coil embolization. The patient tolerated the treatment well. On DSA obtained six months after the first endovascular treatment, coil compaction and recanalization of the aneurysm were detected. A second coil embolization was successfully performed without any complications. The aneurysm was stable during the next six-month follow-up. Stent-assisted coil embolization may be feasible and effective for such postoperatively complicated aneurysms.


Assuntos
Doenças Arteriais Cerebrais/cirurgia , Embolização Terapêutica/métodos , Aneurisma Intracraniano/cirurgia , Stents , Idoso , Angiografia Digital , Prótese Vascular , Doenças Arteriais Cerebrais/complicações , Doenças Arteriais Cerebrais/diagnóstico por imagem , Seguimentos , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Artéria Cerebral Posterior/diagnóstico por imagem , Artéria Cerebral Posterior/cirurgia , Resultado do Tratamento
9.
World Neurosurg ; 92: 339-348, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27188642

RESUMO

OBJECTIVE: To elucidate venous drainage patterns to avoid damage to the venous drainage route in the middle cranial fossa and superior petrosal sinus when employing the transpetrosal approach. METHODS: Venous drainage patterns were assessed using three-dimensional computed tomography venography in 22 hemispheres of petroclival meningioma (PCM) cases from patients who underwent primary surgery and 40 hemispheres of control cases. Intracranial venous drainage patterns were compared between control cases and PCM cases. RESULTS: The proportion of hemispheres with complete and medial superior petrosal sinus drainage patterns was lower in PCM cases. With regard to the superficial middle cerebral vein drainage pattern, the proportion of hemispheres with the cavernous sinus capture type was lower and the proportion with the emissary type was higher in PCM cases. The proportion of hemispheres with multiple greater anastomoses of the superficial middle cerebral vein was higher in PCM cases without the emissary-type and cavernous sinus capture-type patterns. When the venous drainage route of the cavernous sinus capture type and/or emissary type was disturbed, in particular, greater anastomosis via the vein of Labbè and the vein of Trolard was needed to control venous drainage flow. CONCLUSIONS: In cases of venous drainage impairment secondary to PCM progression, the drainage route changed to the pterygoid plexus route through the emissary foramen and/or superior sagittal sinus and to the transverse sinus route through the greater anastomosis of the superficial middle cerebral vein. In the anterior transpetrosal approach, peeling off the dura propria of the trigeminal nerve of the foramen rotundum for petrous apex exposure may be associated with the potential risk of pterygoid plexus drainage route impairment.


Assuntos
Veias Cerebrais/cirurgia , Cavidades Cranianas/cirurgia , Drenagem/métodos , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adolescente , Adulto , Idoso , Circulação Cerebrovascular , Angiografia por Tomografia Computadorizada , Cavidades Cranianas/diagnóstico por imagem , Feminino , Humanos , Imageamento Tridimensional , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Pessoa de Meia-Idade , Osso Petroso/cirurgia , Adulto Jovem
10.
Arthritis Res Ther ; 17: 31, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25811130

RESUMO

INTRODUCTION: CCAAT/enhancer-binding protein ß (C/EBPß) is a transcription factor that is activated in the synovium in rheumatoid arthritis (RA) and promotes expression of various matrix metalloproteinases. In this study, we examined whether C/EBPß mediates the expression of receptor activator of nuclear factor-kappa-B ligand (RANKL) and drives osteoclast formation in primary fibroblast-like synoviocytes (FLS) from RA patients. The cooperation of C/EBPß and activation transcription factor-4 (ATF4) in the regulation of the RANKL promoter was also investigated. METHODS: Immunofluorescence staining was performed for C/EBPß, RANKL, and ATF4 in synovium from RA patients. Adenovirus expression vectors for two major isoforms, C/EBPß-liver-enriched activator protein (LAP) and - liver-enriched inhibitory protein (LIP), or small interfering RNA for C/EBPß, were used to manipulate C/EBPß expression in RA-FLS. RA-FLS over-expressing C/EBPß were co-cultured with peripheral blood mononuclear cells (PBMCs) to test osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. A promoter assay for RANKL, a chromatin immunoprecipitation (ChIP) assay and an immunoprecipitation (IP) assay were also performed. RESULTS: Immunofluorescence staining showed colocalization of C/EBPß, ATF4 and RANKL in RA synovium. Western blotting revealed the expression of C/EBPß-LAP and -LIP in RA-FLS. Over-expression of either C/EBPß-LAP or -LIP significantly increased the expression of RANKL mRNA, while C/EBPß-LIP down-regulated osteoprotegerin (OPG) mRNA. The RANKL/OPG mRNA ratio was significantly increased by C/EBPß-LIP over-expression. Knockdown of C/EBPß with siRNA decreased the expression of RANKL mRNA. The number of TRAP-positive multinucleated cells was increased in co-cultures of PBMCs and FLS over-expressing either C/EBPß-LAP or -LIP, but was more significant with LIP. C/EBPß-LIP does not have a transactivation domain. However, promoter assays showed that C/EBPß-LIP and ATF4 synergistically transactivate the RANKL promoter. ChIP and IP assays revealed the cooperative binding of C/EBPß and ATF4 on the RANKL promoter. CONCLUSIONS: We demonstrated that C/EBPß, especially C/EBPß-LIP in cooperation with ATF4, is involved in osteoclast formation by regulating RANKL expression in RA-FLS. These findings suggest that C/EBPß plays a crucial role in bone destruction in RA joints.


Assuntos
Artrite Reumatoide/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Osteoclastos/metabolismo , Ligante RANK/metabolismo , Membrana Sinovial/metabolismo , Fator 4 Ativador da Transcrição/metabolismo , Adulto , Western Blotting , Imunoprecipitação da Cromatina , Citocinas/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Ligante RANK/genética , Reação em Cadeia da Polimerase em Tempo Real , Membrana Sinovial/citologia
11.
Asian J Neurosurg ; 10(1): 52, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25767585

RESUMO

OBJECTIVE AND BACKGROUND: Unruptured aneurysm surgery is a challenge to all vascular neurosurgeons as the patient is asymptomatic and no even slight neurological deficits should be expected postoperatively. To this aim, multi-modality checking of the vessels during the surgery is highly recommended to assure of the patency of the parent and perforator arteries next to an aneurysm. In this paper, we present our experience in the last 1.5 years with emphasis on the role of endoscope assisted microsurgery. METHODS: One hundred and seventy-five patients with unruptured intracranial aneurysms were operated in our institute in the last 1½ years. All patients underwent endoscope assisted microsurgery with pre- and post-clipping indocyanine green angiography. In selected cases, motor evoked potential monitoring was implemented. RESULTS: No mortality was observed in this period, and only 6 patients (3.4%) suffered new permanent neurological deficits postoperatively. Our illustrative cases show how endoscopy may help the surgeon to visualize hidden vessels behind and medial to an aneurysm. CONCLUSIONS: Our results indicated that multi-modality monitoring during unruptured aneurysm surgeries is associated with excellent outcome. Endoscope is able to show blind corners during aneurysm surgery which cannot be routinely observed with microscope and its application in aneurysm surgery assists the surgeon to make certain of complete neck clipping and preservation of perforating arteries around the aneurysm.

12.
J Orthop Surg Res ; 9: 98, 2014 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-25312099

RESUMO

BACKGROUND: In recent years, several methods have been developed for repairing full-thickness cartilage defects by tissue engineering using mesenchymal stem cells. Most of these use scaffolds to achieve sufficient thickness. However, considering the potential influence of scaffolds on the surrounding microenvironment, as well as immunological issues, it is desirable to develop a scaffold-free technique. In this study, we developed a novel technique, a scaffold-free autologous construct derived from bone marrow-derived mesenchymal stem cells (BM-MSCs), and successfully use this technique to regenerate cartilage and subchondral bone to repair an osteochondral defect in rabbit knees. METHODS: BM-MSCs were isolated from bone marrow liquid aspirated from the iliac crest of rabbits. After expansion in culture dishes and re-suspension in 96-well plates, the cells spontaneously aggregated into a spheroid-like structure. The spheroids were loaded into a tube-shaped Teflon mold with a 5-mm height and maintained under air-liquid interface conditions. These loaded spheroids fused with each other, resulting in a cylinder-shaped construct made of fused cells that conformed to the inner shape of the mold. The construct was implanted into an osteochondral defect in rabbit knees and histologically analyzed 24 and 52 weeks after implantation using Wakitani's scoring system. RESULTS: Both bone and cartilage were regenerated, maintaining a constant thickness of cartilage. The mean histological score was 10 ± 1.7 in the 24-week group and 9.7 ± 0.6 in the 52-week group. There was no significant difference between the 24- and 52-week groups in either parameter of the score, indicating that no deterioration of the repaired tissue occurred during the intervening period. CONCLUSIONS: Using our novel technique, which employs a three-dimensional scaffold-free autologous construct derived from BM-MSCs, we successfully achieved simultaneous regeneration of bone and cartilage for up to 1 year in vivo. This method has potential for clinical use as a safe and effective method for repairing bone and cartilage defects.


Assuntos
Cartilagem Articular/fisiologia , Regeneração Tecidual Guiada/métodos , Células-Tronco Mesenquimais/fisiologia , Engenharia Tecidual/métodos , Animais , Medula Óssea , Células Cultivadas , Feminino , Células-Tronco Mesenquimais/ultraestrutura , Microscopia Eletrônica de Varredura , Coelhos , Tecidos Suporte
13.
PLoS One ; 9(8): e104547, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25105964

RESUMO

BACKGROUND: CCAAT/enhancer binding protein ß (C/EBPß) is a transcription factor that promotes hypertrophic differentiation of chondrocytes. Indian hedgehog (Ihh) also stimulates the hypertrophic transition of chondrocytes. Furthermore, runt-related transcription factor-2 (RUNX2) was reported to regulate chondrocyte maturation during skeletal development and to directly regulate transcriptional activity of Ihh. In this study, we investigated whether the interaction of C/EBPß and RUNX2 regulates the expression of Ihh during chondrocyte differentiation. METHODOLOGY/RESULTS: Immunohistochemistry of embryonic growth plate revealed that both C/EBPß and Ihh were strongly expressed in pre-hypertrophic and hypertrophic chondrocytes. Overexpression of C/EBPß by adenovirus vector in ATDC5 cells caused marked stimulation of Ihh and Runx2. Conversely, knockdown of C/EBPß by lentivirus expressing shRNA significantly repressed Ihh and Runx2 in ATDC5 cells. A reporter assay revealed that C/EBPß stimulated transcriptional activity of Ihh. Deletion and mutation analysis showed that the C/EBPß responsive element was located between -214 and -210 bp in the Ihh promoter. An electrophoretic mobility shift assay (EMSA) and a chromatin immunoprecipitation (ChIP) assay also revealed the direct binding of C/EBPß to this region. Moreover, reporter assays demonstrated that RUNX2 failed to stimulate the transcriptional activity of the Ihh promoter harboring a mutation at the C/EBPß binding site. EMSA and ChIP assays showed that RUNX2 interacted to this element with C/EBPß. Immunoprecipitation revealed that RUNX2 and C/EBPß formed heterodimer complex with each other in the nuclei of chondrocytes. These data suggested that the C/EBPß binding element is also important for RUNX2 to regulate the expression of Ihh. Ex vivo organ culture of mouse limbs transfected with C/EBPß showed that the expression of Ihh and RUNX2 was increased upon ectopic C/EBPß expression. CONCLUSIONS: C/EBPß and RUNX2 cooperatively stimulate expression of Ihh through direct interactions with a C/EBPß binding element, which further promotes hypertrophic differentiation of chondrocytes during the chondrocyte differentiation process.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Condrócitos/citologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteínas Hedgehog/genética , Ativação Transcricional , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Diferenciação Celular , Células Cultivadas , Condrócitos/metabolismo , Condrogênese , Regulação da Expressão Gênica , Camundongos , Regiões Promotoras Genéticas
14.
J Orthop Surg (Hong Kong) ; 18(3): 271-5, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21187533

RESUMO

PURPOSE: To retrospectively evaluate factors leading to total hip arthroplasty (THA) in patients with subchondral insufficiency fractures (SIF) of the femoral head. METHODS. 5 men and 22 women aged 51 to 85 (mean, 72) years with SIF of the femoral head initially underwent conservative treatment. THA was later performed for 13 patients, as the hip pain became worse secondary to joint space narrowing and/ or femoral head collapse. Patient demographics and radiological variables were retrieved. Risk factors leading to THA in patients with SIF of the femoral head were identified. Receiver operating characteristic curves were used to determine optimal cut-off values for the significant risk factors. RESULTS: 2 men and 11 women aged 62 to 85 (mean, 74.9) years underwent THA and were followed up for 0.2 to 62 (mean, 13) months. The remaining 3 men and 11 women aged 51 to 81 (mean, 68) years underwent conservative treatment and were followed up for 9 to 93 (mean, 28) months. Patient age was the only risk factor for THA (p = 0.047, odds ratio = 1.13), the cutoff value being 71 years (sensitivity, 77%; specificity, 64%). The survival rate was significantly lower in patients aged 71 years or older than in those aged younger than 71 years (p < 0.05). CONCLUSION: Elderly patients with SIF of the femoral head are at higher risk of undergoing THA.


Assuntos
Artroplastia de Quadril , Cabeça do Fêmur/lesões , Fixação de Fratura , Fraturas de Estresse/cirurgia , Fraturas do Quadril/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fraturas de Estresse/diagnóstico , Fraturas de Estresse/etiologia , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Fatores de Risco
15.
Clin Orthop Relat Res ; 468(5): 1331-5, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20058110

RESUMO

BACKGROUND: Subchondral insufficiency fracture of the femoral head occurs mainly in elderly patients with osteoporosis. Spontaneous resolution is observed after nonoperative treatment in some patients whereas other show progressive joint destruction requiring THA. Several studies report the occurrence of subchondral insufficiency fracture of the femoral head in dysplastic hips. QUESTIONS/PURPOSES: We asked whether the extent of hip dysplasia or osteoporosis was greater in patients with subchondral insufficiency fracture of the femoral head than in normal control subjects. PATIENTS AND METHODS: We compared the clinical and imaging findings of 13 patients with subchondral insufficiency fractures of the femoral head and 12 patients scheduled for TKA with asymptomatic hips. Age, gender, and body mass index were comparable in the two groups. RESULTS: Higher mean Sharp angles, lower acetabular head indices, lower center-edge angles, and higher acetabular roof angles in patients with subchondral insufficiency fracture of the femoral head than in those with asymptomatic hips suggested a greater degree of hip dysplasia. Bone mineral density and serum levels of Type I collagen cross-linked N-telopeptide and bone alkaline phosphatase were similar in the two groups. CONCLUSIONS: We speculate an excessive amount of stress on the acetabular edge from dysplasia may be associated with the occurrence of subchondral insufficiency fracture of the femoral head.


Assuntos
Fraturas do Colo Femoral/etiologia , Fraturas de Estresse/etiologia , Osteocondrodisplasias/complicações , Osteoporose/complicações , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Índice de Massa Corporal , Densidade Óssea , Colágeno Tipo I/sangue , Diagnóstico Diferencial , Feminino , Fraturas do Colo Femoral/diagnóstico , Fraturas do Colo Femoral/metabolismo , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Seguimentos , Fraturas de Estresse/diagnóstico , Fraturas de Estresse/metabolismo , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/metabolismo , Osteoporose/diagnóstico , Osteoporose/metabolismo , Peptídeos/sangue , Projetos Piloto , Radiografia , Estudos Retrospectivos
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