Synovial sarcoma with ossification and calcification with SS18 immunochemical expression and rearrangement by fluorescent in situ hybridization / Sarcoma sinovial con osificación y calcificación, con expresión de SS18 por inmunohistoquímica y reordenamiento de SS18 por hibridación in situ fluroescente

Synovial sarcoma is a soft tissue tumor of uncertain origin. Generally, it is a monophasic spindle cell neoplasm that can have glandular-like structures. Ossification and presence of calcification is a rare phenomenon with only a few reported cases. We present the case of a young male with a synovial sarcoma of the right foot. Histology revealed prominent deposits of tumoral osteoid and coarse calcifications. The diagnosis was confirmed by the expression of SS18 by immunohistochemistry and the demonstration of the rearrangement of the SS18 gene by fluorescent in situ hybridization. We reviewed the literature for synovial sarcoma with prominent ossification or calcification, and to the best of our knowledge, this is the first case with expression of SS18 by immunohistochemistry. The main differential diagnoses are osteosarcoma (both primary of bone and extraosseous) and sclerosing epithelioid fibrosarcoma.(AU)

El sarcoma sinovial (SS) es un tumor de partes blandas de origen incierto. Generalmente es una neoplasia monofásica de células fusiformes que puede tener estructuras de tipo glandular. La osificación y la presencia de calcificaciones es un fenómeno raro, con pocos casos reportados. A continuación presentamos el caso de un hombre joven con un sarcoma sinovial del pie derecho que en la histología mostró depósitos de osteoide tumoral y calcificaciones gruesas. El diagnóstico fue confirmado por la expresión de SS18 por inmunohistoquímica y la demostración del reordenamiento del gen SS18 por hibridación in situ fluorescente. Revisamos la literatura referente a sarcoma sinovial con osificación o calcificación prominente, y este es el primer caso con expresión de SS18 por inmunohistoquímica. Los principales diagnósticos diferenciales son con osteosarcoma (tanto primario de hueso como extraóseo) y fibrosarcoma epitelioide esclerosante (sclerosing epithelioid fibrosarcoma [SEF]).(AU)

Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo / Desing and comparison of bone substitutes. Study of in vivo behavior in a rabbit model

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

[Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model / Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

LncRNA MALAT1-related signaling pathways in osteosarcoma

Osteosarcoma (OS) is a common and malignant form of bone cancer, which affects children and young adults. OS is identified by osteogenic differentiation and metastasis. However, the exact molecular mechanism of OS development and progression is still unclear. Recently, long non-coding RNAs (lncRNA) have been proven to regulate OS proliferation and drug resistance. LncRNAs are longer than 200 nucleotides that represent the extensive applications in the processing of pre-mRNA and the pathogenesis of human diseases. Metastasis‐associated lung adenocarcinoma transcript‐1 (MALAT1) is a well-known lncRNA known as a transcriptional and translational regulator. The aberrant expression of MALAT1 has been shown in several human cancers. The high level of MALAT1 is involved in OS cell growth and tumorigenicity by targeting several signaling pathways and miRNAs. Hence, MALAT1 might be a suitable approach for OS diagnosis and treatment. In this review, we will summarize the role of lncRNA MALAT1 in the pathophysiology of OS (AU)

Estimación de la osificación de los huesos del pie sobre población extremeña. Estudio observacional / Estimation of the ossification of the bones of the foot about the population of Extremadura. Observational study

Objetivos: La estimación de la edad de un individuo es un tema de interés dentro del ámbito de la Medicina Legal y Forense. Una de las herramientas más utilizadas para este fin es la Radiología. Los objetivos son la cuantificación de las edades de osificación de cada hueso del pie y determinar si existe relación entre la osificación de los huesos y el sexo del individuo. Pacientes y métodos: La población de estudio se compuso de 2476 radiografías digitales, pertenecientes a un total de 816 sujetos en periodo de crecimiento. El análisis de las imágenes se realizó mediante la aplicación del método validado y diseñado para la estimación de la edad en meses sobre la radiografía del esqueleto del pie.Resultados: Sí existe diferencia en la osificación ósea de la población extremeña frente a la literatura (p valor < 0.05). Todos los huesos que forman el Tarso poseen significación estadística en la comparación por sexos a excepción del cuboides, el cuneiforme medial y el cuneiforme lateral. Conclusiones: Sí existe diferencia significativa en la osificación de hueso del pie entre sexos y entre poblaciones de diferente raza.(AU)

Objectives: The estimation of the age of an individual is a topic of interest within the field of Legal and Forensic Medicine. One of the most used tools for this purpose is Radiology. The objectives of the present work are the quantification of the ages of ossification of each bone of the foot and to determine if there is a relationship between the ossification of the bones and the sex of the individual.Patients and methods: The study population was made up of 2476 digital radiographs, belonging to a total of 816 subjects in the growth period. The analysis of the images was carried out by applying the method validated and designed for the estimation of age in months on the X-ray of the skeleton of the foot. Results: If there is a difference in the bone ossification of the population of Extremadura compared to the literature (p value < 0,05). All the bones that form the tarsus have statistical significance in the comparison by sex, except for the Cuboid, the Medial Cuneiform and the Lateral Cuneiform. Conclusions: If there is a significant difference in foot bone ossification between sexes and between populations of different races.(AU)

RNA-sequencing of human aortic valves identifies that miR-629-3p and TAGLN miRNA-mRNA pair involving in calcified aortic valve disease

This study aimed to uncover the microRNA and messenger RNA (miRNA/mRNA) interactions in the pathophysiological process of calcified aortic valve disease (CAVD) of the human aortic valve. RNA sequencing of six selected samples (3 healthy control samples vs. 3 CAVD samples) was performed to obtain mRNA and miRNA sequences, and differential expression (DE) analysis of miRNA and mRNAs was performed. To build a CAVD-specific miRNA-mRNA interactome, the upregulated mRNAs and downregulated miRNAs were selected, followed by the establishment of inverse DE of mRNA-miRNA co-expression network based on Pearson’s correlation coefficient using miRanda in the R language software. Subsequently, pathway enrichment analysis was performed to elucidate CAVD-related pathways that were likely mediated by miRNA regulatory mechanisms. In addition, miRNAs with an mRNA correlation greater than 0.9 in the co-expression network were selected for anti-calcification verification in a CAVD cellular model. We identified 216 mRNAs (99 downregulated and 117 upregulated) and 602 miRNAs (371 downregulated and 231 upregulated) that were differentially expressed between CAVD and healthy aortic valves. After applying Pearson’s correlation toward miRNA-mRNA targets, a regulatory network of 67 miRNAs targeting 76 mRNAs was created. The subsequent pathway enrichment analysis of these targeted mRNAs elucidated that genes within the focal adhesion pathway are likely mediated by miRNA regulatory mechanisms. The selected hsa-miR-629-3p and TAGLN pair exhibited anti-calcification effects on osteogenic differentiation-induced human aortic valve interstitial cells (hVICs). On integrating the miRNA and mRNA sequencing data for healthy aortic valves and those with CAVD, the CAVD-associated miRNA-mRNA interactome and related pathways were elucidated. (AU)

circ-CCND1 regulates the CCND1/P53/P21 pathway through sponging miR-138-5p in valve interstitial cells to aggravate aortic valve calcification

To discuss the effect and mechanism of circular-CCND1 (circ-CCND1) on the regulation of calcified aortic valve disease (CAVD). Differentially expressed circRNAs were screened through the GSE155119 data set and biological prediction. Subsequently, the miR-138-5p, CCND1, and circ-CCND1 expression were detected in the non-calcified and calcified aortic valve. Then Pearson correlation analysis was performed to analyze the correlation between the above expression, and dual luciferase and RNA-pull down assays for verifying the target relationship. Porcine aortic valve interstitial cells (AVICs) were isolated and transfected with pcDNA-circ-CCND1, miR-138-5p inhibitor, and miR-138-5p mimics. The alkaline phosphatase (ALP) activity was quantitatively analyzed by ALP staining, and alizarin-red staining was to check the calcium nodules formation. Finally, Western blot was applied to detect the expression of proteins associated with osteogenic differentiation (Runx2, Osterix, OPN) and CCND1/P53/P21 pathway proteins. Circ-CCND1 was highly expressed in calcific aortic valves. After inhibiting circ-CCND1 expression, a significant reduction was shown in ALP activity, the degree of ossification and the formation of calcium nodules in AVICs, and osteogenic differentiation-related protein expression and CCND1/P53/P21 pathway protein expression. By contrast, inhibition of miR-138-5p and circ-CCND1 together promoted the calcification of AVICs and expression of CCND1/P53/P21 pathway proteins. P53 inhibitor (PFT-α) could significantly reduce activation of CCND1/P53/P21 pathway protein expression by circ-CCND1 overexpression. However, P53 activator (Nutlin-3) significantly restored the suppression of the above pathway-related protein expression by downregulation of circ-CCND1. Circ-CCND1 sponges miR-138-5p to regulate CCND1 expression, thereby promoting the calcification of AVICs. (AU)

TLR4 activation inhibits the proliferation and osteogenic differentiation of skeletal muscle stem cells by downregulating LGI1

Skeletal muscle stem cells (SMSCs) are vital to the growth, maintenance, and repair of the muscles; emerging evidence has indicated that Toll-like receptor 4 (TLR4) can potentially regulate muscle regeneration. In present study, in vitro and in vivo experiments were performed to explore the correlation of TLR4 with leucine-rich glioma-inactivated 1 (LGI1) as well as their effects on the proliferation and osteogenesis potential of SMSCs. In order to examine the regulatory mechanisms of TLR4 and LGI1 in SMSCs, the obtained cells were treated with lipopolysaccharide (LPS, used as an activator of TLR4) of different concentration at different time points as well as the siRNA against LGI1. Subsequently, a series of detection was undertaken in order to measure the proliferation and differentiation potential of SMSCs, which involved detection of the related factors, cell activity, and the sphere-forming capability. Following LPS treatment, the increased TLR4 expression and reduced LGI1 expression were observed. Consequently, we also discovered that Erk signaling pathway was inactivated and cell proliferation and osteogenesis capabilities declined, presented by the downregulation of related factors such as cyclin B1 and runt-related transcription factor 2. Moreover, the cell activity and sphere-formation performance of SMSCs were also declined. These results were also validated in rats with cecal ligation and perforation-induced rat models with sepsis. In conclusion, the present study reveals a regulatory mechanism in SMSCs whereby LGI1 expression is reduced by TLR4, thus impeding cell proliferation and osteogenesis, highlighting TLR4 as a potential therapeutic target against many diseases related to SMSCs. (AU)

Evaluación de maduración de sutura palatina mediana con el método de Angelieri et al. Revisión narrativa / Evaluation of the maturation of midpalatal suture with the Angelieri's method. Narrative review

Introducción: Evaluar la maduración de la sutura palatina mediana (SPM) es importante en ortodoncia y ortopedia dentofacial, para decidir el tipo de tratamiento para expansión palatina, en pacientes con compresión maxilar. Angelieri et al. el 2013, proponen un método de evaluación de maduración de la SPM con tomografía computarizada de haz cónico. No se encontraron publicaciones que analicen artículos que describen y aplican el método de Angelieri. El propósito de esta revisión es analizar el método de Angelieri, describiendo usos, ventajas y desventajas. Revisión: El método de Angelieri clasifica la maduración de la SPM en 5 etapas (A-E). Su uso complementa a estudios con radiografías convencionales cuando éstas indican que el paciente está en etapas circumpuberales y post peak puberal. La identificación de la etapa de maduración de la SPM permite determinar las alternativas de tratamiento -ortopédico o con enfoque quirúrgico-, de acuerdo a si la SPM está sin osificación o con osificación parcial/total, respectivamente. Algunas ventajas del método de Angelieri son ser un método no invasivo, y reproducible tras una adecuada formación. Una de sus desventajas es la falta de un gold standard que compruebe que la morfología imagenológica de la SPM propuesta por los autores no es solo teórica. Conclusiones: El método de Angelieri es útil para evaluar la maduración de la SPM, previa calibración. No existe acuerdo en que el método de Angelieri sea predictor de éxito del tratamiento para expansión palatina. Se requiere mayor investigación acerca de la contribución de este método para su uso clínico. (AU)

Introduction: Assessing the maturity of the midpalatal suture (MPS) is important in orthodontics and dentofacial orthopedics, to decide the type of treatment for palatal expansion, in patients with maxillary compression. Angelieri et al. in 2013, proposed a method for evaluating the maturation of MPS with cone-beam computed tomography. No publications were found which analyze articles describing and applying the Angelieri's method. The purpose of this review is to analyze the Angelieri's method, describing its uses, advantages and disadvantages.Review: Angelieri's method classifies MPS maturation into 5 stages (A-E). Its use complements studies with conventional bi-dimensional radiographs, when they indicate the patient is in circumpubertal and post-peak pubertal stages. The identification of the stage of maturation of MPS allows to determine the treatment alternatives -orthopedic or with a surgical approach-according to whether MPS is without ossification or with partial/total ossification, respectively. Some advantages of the Angelieri's method are being a non-invasive method, and reproducible after adequate training. One of its disadvantages is the lack of a gold standard that proves the imaging morphology of MPS proposed by the authors is not only theoretical.Conclusions: Angelieri's method is useful to evaluate the maturation of MPS, after calibration. There is no agreement that Angelieri's method is a predictor of treatment success for palatal expansion. Further research is required on the contribution of this method to its clinical use. (AU)

Modulatory activity of a bovine hydrolyzed collagen-hydroxyapatite food complex on human primary osteoblasts after simulating its gastrointestinal digestion and absorption / Actividad moduladora de un complejo alimentario de colágeno hidrolizado e hidroxiapatita bovinos sobre osteoblastos primarios humanos tras simular su digestión gastrointestinal y su absorción

Introduction: osteoporosis is the most prevalent bone disease and one of the main causes of chronic disability in middle and advanced ages. Conventional pharmacological treatments are still limited, and their prolonged use can cause adverse effects that motivate poor adherence to treatment. Nutritional strategies are traditionally based on supplementing the diet with calcium and vitamin D. Recent studies confirm that the results of this supplementation are significantly improved if it is accompanied by the intake of oral hydrolyzed collagen. Objective: to evaluate the possible in vitro osteogenic activity of a peptide-mineral complex formed by bovine hydrolyzed collagen and bovine hydroxyapatite (Phoscollagen®, PHC®). Methods: the digestion and absorption of PHC® were simulated using the dynamic gastrointestinal digester of AINIA and Caco-2 cell model, respectively. Primary cultures of human osteoblasts were treated with the resulting fraction of PHC® and changes were evaluated in the proliferation of preosteoblasts and in the mRNA expression of osteogenic biomarkers at different stages of osteoblast maturation: Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin (OC) and type I collagen (ColA1). Results: an increase in preosteoblastic proliferation was observed (p ≤ 0,05). No changes were detected in the biomarkers of osteoblasts with 5 days of differentiation, but with 14 days, registering in this case an increase in Runx2 (p = 0.0008), ColA1 (p = 0.035), OC (p = 0.027) and ALP (without significance). Conclusion: these results show that PHC® peptide-mineral complex stimulates the activity of mature osteoblasts, being capable of promoting bone formation (AU)

Introducción: la osteoporosis es la enfermedad ósea más prevalente y una de las principales causas de discapacidad crónica en las edades medias y avanzadas. Los tratamientos farmacológicos convencionales aún son limitados y su uso prolongado puede provocar efectos adversos que motiven baja adherencia al tratamiento. Las estrategias nutricionales se basan tradicionalmente en suplementar la dieta con calcio y vitamina D. Estudios recientes confirman que los resultados de esta suplementación mejoran significativamente si se acompaña de la ingesta de colágeno hidrolizado oral. Objetivo: evaluar la posible actividad osteogénica in vitro de un complejo péptido-mineral formado por colágeno hidrolizado e hidroxiapatita bovinos (Phoscollagen®, PHC®). Métodos: se simuló la digestión y absorción de PHC® utilizando el digestor dinámico gastrointestinal de AINIA y el modelo celular Caco-2, respectivamente. Cultivos primarios de osteoblastos humanos se trataron con la fracción resultante de PHC® y se evaluaron los cambios en la proliferación de los preosteoblastos y en la expresión del ARNm de los biomarcadores osteogénicos en diferentes etapas de maduración de los osteoblastos: factor de transcripción 2 relacionado con Runt (Runx2), fosfatasa alcalina (ALP), osteocalcina (OC) y colágeno tipo I (ColA1). Resultados: se observó un incremento de la proliferación preosteoblástica (p ≤ 0,05). No se detectaron cambios en los biomarcadores de osteoblastos con 5 días de diferenciación, pero sí con 14 días, registrándose un aumento de Runx2 (p = 0,0008), ColA1 (p = 0,035), OC (p = 0,027) y ALP (sin significancia). Conclusión: estos resultados muestran que el complejo péptido-mineral PHC® estimula la actividad de osteoblastos maduros, siendo susceptible de promover la formación ósea (AU)

Coronectomía en terceros molares inferiores / Coronectomy of the lower third molar

La extracción del tercer molar inferior es el procedimiento más frecuente dentro del campo de la cirugía bucal, siendo el daño del nervio dentario inferior una de las complicaciones más frecuentes en la extracción. Como alternativa para disminuir el riesgo de aparición de esta complicación surge la coronectomía, técnica que consiste en la eliminación de la corona dentaria manteniendo intactas las raíces dentro del hueso alveolar. El objetivo del presente artículo fue realizar una puesta al día sobre la coronectomía en terceros molares inferiores, analizando indicaciones, contraindicaciones, complicaciones y éxito de esta técnica. La coronectomía parece ser una alternativa eficaz a la extracción para la prevención de trastornos neurosensoriales en terceros molares impactados en estrecha relación con el NDI. Sin embargo, es necesaria la realización de más estudios comparando la extracción convencional con la coronectomía, con un mayor seguimiento, para conocer el éxito y las complicaciones a largo plazo de este tratamiento

The lower third molar extraction is one of the most common procedures in the field of oral surgery. Furthermore, the damage of the inferior alveolar nerve is one of the most frequent complications related to this procedure. The coronectomy was introduced in 1984, as an alternative approach that tended to reduce the occurrence of this complication. The main objective of this article is to review current evidence of coronectomy applied to mandibular third molars, analyzing indications, contraindications, complications and success of the technique. The coronectomy seems to be an effective alternative to conventional third molar extraction, for the prevention of neurosensorial disorders in impacted third molars in direct relation with inferior alveolar nerve. However, further studies are needed which compare conventional approach with coronectomy with a greater follow-up to understand the long-term morbidities and success of the technique

Capacitación osteogénica in vitro de células madre mesenquimales de médula ósea para su aplicación en resecciones segmentarias de hueso / Osteogenic in vitro training of bone marrow mesenquimal cells for application in segmentary bone resections

OBJETIVO: Obtener continuidad ósea en un modelo experimental de resección segmentaria en la diáfisis del fémur mediante tratamiento con células mesenquimáticas indiferenciadas comprometidas al linaje osteogénico. MATERIAL Y MÉTODO: Se obtuvieron células mesenquimáticas indiferenciadas a partir de médula ósea de ratas Wistar singénicas, se diferenciaron al linaje osteogénico y se embebieron en bloques de hidroxiapatita. Se implantaron en una resección segmentaria en la diáfisis del fémur, que se sintetizó con una placa de 1,5mm de grosor. Se calcularon distribuciones binomiales estableciéndose un grupo experimental y 3 de control, constituidos por 8 elementos cada grupo. Grupo I, relleno con aloinjerto; grupo II, con hidroxiapatita; grupo III, con hidroxiapatita embebida con células osteocomprometidas; grupo IV con células osteocomprometidas mediante cultivo tridimensional. Se realizó estadística descriptiva con distribución de frecuencias mediante la prueba de Fisher, considerándose significativo el valor de p < 0,05. RESULTADOS: El grupo I presentó buena consolidación, sin rotura de placas. El grupo II mostró tejido fibroso y rotura de todas las placas. El grupo III mostró tejido óseo, pero en todos los casos se rompieron las placas. El grupo IV mostró consolidación sin rotura de placas. CONCLUSIÓN: La terapia mediante células mesenquimáticas indiferenciadas en cultivos tridimensionales produce tejido óseo y asegura una estabilización mecánica permanente. Limitaciones: antes de la inferencia humana es necesario realizar el experimento en grupos con más elementos

OBJECTIVE: To achieve bone continuity in an experimental model of segmental resection of femur bone by applying a treatment with committed to osteogenic bone linage mesenchymal stem cells. MATERIAL AND METHOD: Bone marrow mesenchymal stem cells, obtained from syngeneic Wistar murine, were committed into osteogenic lineage and embedded within a hydroxipatite block. They were implanted in an experimentally created diaphyseal femur resection model. The diaphysis was synthetized with a 1.5mm thick plate. In order to calculate binomial distributions, we stablished one experimental and 3 control groups of 8 elements each: Group I, filling the gap with allograft; group II, filling with a hydroxyapatite block without cells; group III, filling with the hydroxyapatite block embedded with committed cells, and group IV, with the hydroxyapatite embedded with osteoinduced cells in a 3 dimensions TRAP culture. Descriptive analysis was performed by frequency distribution and Fisher statistic test. Level of statistical significance was considered at P<.05. RESULTS: Group I presented good bone consolidation and no plate breakage. Group II showed fibrous but non-bone tissue, with rupture of all plates. Group III showed bone tissue in all cases, but the plates broke in all of them, while in group IV bone consolidation was achieve without any plate rupture. CONCLUSION: Cell therapy with mesenchymal stem cells, trained in a 3 dimensions cell culture, produces bone tissue and ensures the permanence of the mechanical stabilization performed in a segmental resection model. Limitations: A study with a larger sample size is necessary before planning the human inference

Incidencia de la hiperostosis esquelética difusa idiopática sobre un modelo clínico de disfagia / Incidence of diffuse idiopathic skeletal hyperostosis from a model of dysphagia

OBJETIVO: Relacionar la clínica de disfagia con la enfermedad de Forestier-Rotes-Querol o hiperostosis esquelética difusa idiopática (HEDI), desorden por osificación del ligamento cervical anterior común y calcificaciones en otras articulaciones. PACIENTES Y MÉTODOS: Revisión del historial clínico-radiológico de 455 pacientes que en 5 años consultaron en nuestro centro por disfagia, remitidos desde Atención Primaria o diferentes especialidades. El diagnóstico de HEDI se estableció en función de los criterios descritos por Resnick. RESULTADOS: Sobre un volumen total de 32.544 pacientes atendidos, el 1,4% consultó por disfagia alta. En 51 casos con esta sintomatología -el 11,2% de los sujeto- pudieron verificarse datos congruentes con los hallazgos radiológicos diagnósticos de HEDI. La incidencia observada fue de 7:100.000 habitantes-año. Dos casos con disfagia severa mejoraron con la retirada del hueso cervical neoformado. CONCLUSIONES: La HEDI supone una osificación interarticular anquilosante habitualmente sistémica pero asintomática. Al manifestarse, distorsiona principalmente las funciones de cuello y vías altas, generando sobre todo disfagia. Unos pocos casos requieren cirugía liberadora de estas calcificaciones

OBJECTIVE: To relate symptoms of dysphagia to Forestier-Rotes Querol disease or diffuse idiopathic skeletal hyperostosis (DISH), a disorder due to ossification in the anterior longitudinal ligament and calcifications in other entheses. PATIENTS AND METHODS: Review of clinical and radiological findings in 455 outpatients attended at our Centre with dysphagia, for 5 years, referred from dental, trauma, neurological or primary health care. A diagnosis of DISH was established using Resnick's criteria. RESULTS: We detected 51 cases with dysphagia consistent with DISH diagnostic criteria - 11.2% of subjects suffering this symptom- out of 32544 outpatients attended. An incidence of 7:100000 inhabitants per year was observed. Two cases showed significant improvement after removing the new bone in the spine. CONCLUSIONS: DISH is an ankylosing ossification between the joints, frequently systemic but showing no clinical symptoms. When symptoms manifest, neck movements and upper airways are involved, mainly dysphagia. A few cases need surgery to relieve the calcification processes

Osteogenic parameters surrounding trabecular tantalum metal implants in osteotomies prepared via osseodensification drilling

BACKGROUND: Surgical fixation of implants into bone for the correction of bone deformities or defects is a traditional approach for skeletal stabilization. Important measures of efficacy of implants include implant stability and osseo integration-the direct interaction between living bone and an implant. Osseointegration depends on successful implant placement and subsequent bone remodeling. This study utilized osseo densification drilling (OD) in a low bone density model using trabecular metal (TM) implants. MATERIAL AND METHODS: Three osteotomy sites, Regular, OD-CW (clockwise), and OD-CCW (counterclockwise), were prepared in each ilium of three female sheep. Drilling was performed at 1100rpm with saline irrigation. Trabecular metal (TM) (Zimmer(R), Parsippany, NJ, USA) implants measuring 3.7mm in diameter X 10mm length were placed into respective osteotomies. A three-week period post-surgery was given to allow for healing to take place after which all three sheep were euthanized and the ilia were collected. Samples were prepared, qualitatively and quantitatively analyzed using histology micrographs and image analysis software (ImageJ, NIH, Bethesda, MD). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were quantified to evaluate the osseointegration parameters. RESULTS: All implants exhibit successful bone formation in the peri-implant environment as well as within the open spaces of the trabecular network. Osseointegration within the TM (quantified by %BIC) as a function of drilling technique was more pronounced in OD samples (p > 0.05). The %BAFO however shows a significant difference (p = 0.036) between the CCW and R samples. Greater bone volume and frequency of bone chips are observed in OD samples. CONCLUSION: The utilization of OD as a design for improved fixation of hardware was supported by increased levels of stability, both primary and secondary. Histological data with OD provided notably different results from those of the regular drilling method

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Utilización de dentina autógena como material de injerto en Cirugía Bucal / Autogenous dentine as graft material in Oral Surgery

Las extracciones dentarias producen una pérdida ósea en sentido horizontal y vertical, que conllevan alteraciones funcionales para los pacientes, y dificultan la colocación de implantes dentales para los profesionales. Para minimizar esta pérdida ósea, se utilizan diferentes materiales de injerto, entre los cuales destaca el injerto autógeno, por cumplir las características de osteogénesis, osteoconducción y osteoinducción. En el año 2010 se describe por primera vez la utilización de dentina como material de injerto autógeno, demostrando que este material puede ser una alternativa terapéutica al resto de materiales de injerto, al permitir la osteoconducción y la osteoinducción, y mostrar la formación de hueso nuevo en un 46-87% del área con injerto de dentina autógena, 3 meses después de su utilización. La última revisión sistemática publicada en el año 2018, concluyó que los implantes colocados en áreas regeneradas en zonas en las que se empleó dentina como material de injerto, presentaron tasas de supervivencia del 97,7% después de 1 año de seguimiento, sugiriendo este nuevo material como una alternativa con resultados prometedores, aunque son necesarios más estudios al respecto

Subsequent to tooth extraction, a reduction of the length and width of alveolar ridge can be observed. It causes functional alterations to patiens, and problems to proper insertion of dental implants. In order to prevent this bone atrophy, different graft materials can be used, being considered autogenous graft the best because allows osteogenesis, osteoconduction and osteoinduction. In 2010 it was first published the use of autogenous dentine as a graft material, showing it could be an ideal graft material, as a material with excellent osteoconduction and osteoinduction. Besides, this graft material is slowly absorbed and replaced by new bone, in 46-87% of the áreas grafted with dentine, 3 months after regeneration. Last systematic review published in 2018 concluded dental implants inserted in regenerated areas with autogenous dentine had survival rates of 97,7% for over a year follow-up, so this new material is considered an alternative with good results, but there are necessary more studies with long term follow-up

Células osteogénicas afectadas por los factores solublestumorales contribuyen a la formación del nichopre-metastásico óseo / Osteogenic cells affected by soluble tumor factorscontribute to bone pre-metastatic niche formation

Objetivo: Analizar el efecto de los secretomas de tumores sólidos organotrópicos hacia el hueso en células de linaje osteogénico, de tipo osteoblástico y osteocítico, en la expresión de genes relacionados con el metabolismo óseo. Material y método: Caracterizamos los cambios en expresión génica por PCR cuantitativa a tiempo real del eje OPG/RANKL, así como de otros genes relacionados con la diferenciación osteoblástica como son Runx2 y osteocalcina, inducidos por los medios condicionados de células tumorales prostáticas, mama y melanoma en pre‐osteoblastosMC3T3‐E1 y osteocitos MLO‐Y4 murinos o en osteoblastos humanos, según correspondiese por especie. Resultados: La estimulación de las células osteocíticas con medios condicionados de células de melanoma o adenocarcinoma prostático indujo un incremento en la expresión génica de OPG y también de RANKL, viéndose incrementado la ratio OPG/RANKL. Únicamente el secretoma de las células de adenocarcinoma prostático alteró la expresión de Runx2en osteocitos. Los medios condicionados de células de cáncer de mama modificaron únicamente la expresión de RANKLen células osteoblásticas, viéndose disminuido la ratioOPG/RANKL. Conclusión: Los factores solubles tumorales tienen como diana celular a las células osteocíticas, favoreciendo la inducción de un nicho pre‐metastásico óseo por modificación de la ratio OPG/RANKL en el entorno óseo, y, con ello, la progresión de tumores organotrópicos óseos como son el melanoma y adenocarcinomas prostático

Objective: To analyze the effect of the secrets of solid organotropic tumors towards bone in osteogenic, osteoblastic and osteocytic lineage cells, in the expression of genes related to bone metabolism. Material and method: We characterize the changes in gene expression by quantitative real‐time PCR of the OPG/RANKL axis, as well as other genes related to osteoblastic differentiation such as Runx2 and osteocalcin, induced by the conditioned means of prostate tumor cells, breast and melanoma in pre MC3T3‐E1 osteoblasts and murine MLO‐Y4 osteocytes or in human osteoblasts, as appropriate by species. Results: Stimulation of osteocitic cells with conditioned means of melanoma or prostate adenocarcinoma cells inducedan increase in OPG and RANKL gene expression, with the OPG/RANKL ratio being increased. Only the secretome of prostate adenocarcinoma cells altered the expression of Runx2 in osteocytes. Conditioned media of breast cancer cellsonly modified the expression of RANKL in osteoblast cells, with a decrease in OPG/RANKL ratio. Conclusion: Soluble tumor factors have osteocitic cells as their cellular target, favoring the induction of a pre‐metastatic bone niche by modifying the OPG/RANKL ratio in the bone environment, and, thus, the progression of bone organo‐tropic tumors such as melanoma and prostatic adenocarcinomas

Abordaje quirúrgico temprano de la trigonocefalia / Early quirurgic management of trigonocephaly

Introducción y objetivo. La trigonocefalia, originada por la sinostosis prematura de la sutura metópica, en sus formas más graves presenta mayor restricción del crecimiento lateral de los huesos frontales y temporales, afectando a los rebordes supraorbitarios, limitando el crecimiento y condicionando un hipoteleorbitisimo aparente. Los principales problemas de las técnicas quirúrgicas empleadas para su tratamiento son: falta de corrección del defecto, vaciamiento temporal, daño de suturas no afectadas al hacer transposiciones que producen defectos de crecimiento (sinostosis secundarias), sobrecorrección del hipoteleorbitisimo y defectos óseos. El objetivo de este trabajo es presentar nuestra experiencia en una serie de casos tratados de forma temprana con modificaciones propias a las técnicas abiertas propuestas por Dhellemmes en Francia. Material y método. Entre 2010 y 2018 operamos 7 pacientes con trigonocefalia no sindrómica severa, con una media de 7 meses de edad. Todos fueron estudiados con tomografía computerizada de cráneo con reconstrucción ósea en tres dimensiones (TCC-3D) preoperatoria, postoperatoria inmediata y al año de evolución, electroencefalograma, valoración del neurodesarrollo y por Pediatría y Oftalmología. Resecamos la sutura metópica estenosada y efectuamos craneotomías frontales en forma de alas de escarabajo respetando la sutura coronal. Remodelamos la barra frontoorbitaria con injerto óseo para corregir la angulación y la fijamos con un injerto de hueso. Finalmente practicamos osteotomías radiadas en parietal para modificar la restricción del crecimiento de la bóveda. Resultados. Los resultados funcionales y estéticos fueron excelentes, sin defectos de osificación ni vacío de la fosa temporal, ni morbimortalidad, con cicatriz oculta por el cabello. El desarrollo neurocognitivo de los niños tuvo una mejoría notable de la irritabilidad y de la actividad e interacción con los padres. Conclusiones. En trigonocefalia, la cirugía temprana logra la corrección total del defecto en un solo tiempo quirúrgico, obteniendo una remodelación ósea y un crecimiento armónico del cráneo al respetar el crecimiento del sistema suturario. Las modificaciones a la técnica que proponemos evitan el defecto de vaciamiento temporal y permiten no utilizar material de osteosíntesis

Background and objective. The premature synostosis of the metopic suture in the most severe forms occurs with a restriction of the lateral growth of frontal and temporal bones, affecting the supraorbital rims, which limits its growth and leads to hypoteleorbitism. The triangular shape of the forehead is accentuated by the compensatory growth of the other structures of the skull. The main problem of the handling techniques are: temporal emptying, lack of defect correction, damage of unaffected sutures while making transpositions that will later produce defects in growth and cranial molding. Our aim is to show our surgical experience operated with the variations of the open technique that was conceived by Dhellemmes in France. Methods. Between 2010 and 2018 we operated 7 patients with trigonocephaly; patients' average age was 7 months. They were studied with presurgical and post operatory CBT-3D, electroencephalograms, neurodevelopmental assessment and by Pediatry and Ophthalmology. Stenosed metopic suture was resected and frontal craniotomies shaped like beetle wings were performed out without drying the coronal suture, securing them to the fronto-orbital bar with a discreet progress of the side edges. The medial osteotomy of the orbital toolbar was used to reshape it and correct its angulation fixing it with a bone graft and radiated parietal osteotomy to modify the restriction of frontoparietal growth. Results. Functional and aesthetic results were excellent, without ossification defects or vacuum the temporal fossa, morbidity or mortality, with the scar hidden by hair. Children's neuropsychological development had a noticeable improvement in irritability, activity and interaction with their rents. Conclusions. In trigonocephaly, early surgery achieves total defect correction in a single procedure and a bone remodeling and harmonic skull growth by respecting the sutures system. Our modifications to the technique avoid the temporary emptying defect and don't use osteosynthesis material

Bases fisiopatológicas de la neoformación en las espondiloartritis / Physiopathological foundations of neoformation in spondyloarthritis

Una de las características patogénicas de las espondiloartritis (EspA) es la neoformación ósea. Distintos estudios han puesto de manifiesto que el origen de este proceso está en las entesis, donde algunos factores desen cadenantes, como el estrés biomecánico, en un individuo genéticamente predispuesto producirían una compleja cascada de señales que favorecería la vasodilatación local y la activación de células inmunocompetentes residentes. Estas, a su vez, provocarían una respuesta inflamatoria caracterizada por la secreción de factor de necrosis tumoral alfa e interleucina 17 (IL-17), entre otros, y reclutamiento de otras células inmunocompetentes. Además, se ha demostrado que la IL-17 y la IL-22 favorecen la proliferación de células madre mesenquimatosas del periostio perientesítico, lo que lleva a la formación de hueso nuevo en la entesis. En las EspA, la formación de hueso nuevo es principalmente ortotópica (en continuidad con el hueso existente) y se origina a partir de la entesis y del periostio. Al parecer, la mayoría de la neoformación ósea se produce mediante osificación endocondral. En la osificación endocondral, las células progenitoras mesenquimatosas se diferencian en condrocitos, que construyen un «molde» de cartílago, en el cual las células progresivamente maduran y evolucionan hacia condrocitos hipertróficos. Esta matriz es invadida por vasos y precursores osteoblásticos que reemplazan progresivamente el modelo por hueso maduro

One of the pathogenic characteristics of spondyloarthritis (SpA) is bone neoformation. Several studies have revealed that this process originates in the enthesis, in which triggering factors such as biomechanical stress in genetically predisposed individuals may produce a complex cascade of signals favouring local vasodilation and activation of resident immune cells. These in turn induce an inflammatory response characterised by secretion of TNF-alfa and IL-17 (among other substances) and recruitment of other immune cells. In addition, it has been demonstrated that IL-17 and IL-22 favour the proliferation of mesenchymal stem cells of the peri-enthesic periosteum, leading to the formation of new bone in the enthesis. In SpA, new bone formation is mainly orthotopic (in continuity with existing bone) and arises from the enthesis and periosteum. Most bone neoformation seems to occur through endochondral ossification. In this process, mesenchymal progenitor cells differentiate towards chondrocytes, which construct a cartilaginous "mould" in which the cells progressively mature and develop towards hypertrophic chondrocytes. This matrix is invaded by vessels and osteoblastic precursors that progressively replace the model with mature bone

Eficacia del método Ponseti en el tratamiento del pie equinovaro / Ponseti method efficacy in treatment of clubfoot

Contexto: El pie equinovaro es una deformidad musculoesquelética congénita caracterizada por la presencia de cavo, varo, adducto y equino. Afecta a 1-7 de cada 1000 nacimientos. Un pie zambo no tratado puede generar dolor y discapacidad durante la vida de la persona. El método Ponseti se ha convertido en la principal modalidad de tratamiento para el manejo del pie zambo produciendo buenos resultados a largo plazo. El objetivo de este manuscrito fue evaluar la eficacia del método Ponseti y la evolución de los pacientes en función de las tasas de recurrencia, tenotomías y cirugías asociadas. También se determinó si la edad de los niños influía en el éxito del tratamiento. Métodos: Se realizó una estrategia de búsqueda a través de Pubmed hasta abril de 2018. Los términos de búsqueda incluyeron pie zambo, método Ponseti y pie equinovaro. Se incluyeron metaanálisis, revisiones sistemáticas, ensayos clínicos y series de casos. También se examinaron las referencias bibliográficas de los artículos seleccionados. Resultados: Veintisiete artículos fueron incluidos en esta revisión. La literatura actual muestra una tasa de éxito del 78-92% utilizando el método Ponseti. Conclusión: El método Ponseti ofrece resultados alentadores en términos funcionales y estéticos, así como disminución del grado de corrección quirúrgica cuando los resultados no sean los esperados. Se necesita más investigación para generar evidencia de mayor calidad con mayores tamaños muestrales y unificación a la hora de medir la severidad de la deformidad. Otra limitación encontrada fue la ausencia de la definición de fracaso de tratamiento y sus correspondientes motivos

Background: Clubfoot is a congenital musculoskeletal deformity characterized by heel varus, indfoot equinus, mid-foot cavus and forefoot adduction. It is the most common defect that affects between 1 and 7 births in every 1000. Left untreated, clubfoot may lead to pain and disability throughout the person ́s life. Ponseti method has become the main treatment modality for the management of clubfoot producing good long-term results. The aim of this manuscript was to determine the efficacy of the Ponseti method for the treatment of CTEV and to evaluate the evolution of patients based on the recurrence rate, tenotomies rates and surgeries. Also determine if the age of children influences the success of the treatment. Methods: A search strategy completed examined Pubmed from inception to April 2018. Search terms included clubfoot, Ponseti method and equinovarus. Meta-analysis, systematic reviews, randomized control trials and case series were included. The reference lists of the selected articles were also examined. Results: Twenty-seven articles were included in this review. The current literature shows a success of the Ponseti method of 78-92%. Conclusion: Ponseti treatment for clubfoot has encouraging results in terms of attaining a functionally and cosmetically foot and lessening the extent of surgical correction in cases in which it does not reach the expected results. Further research is needed to generate higher quality evidence with larger sample sizes hich evaluate the severity of the deformity with the same measures. Another lack was the absence of a definition of treatment failure with the reasons

CypD-mPTP axis regulates mitochondrial functions contributing to osteogenic dysfunction of MC3T3-E1 cells in inflammation

Bone is a dynamic organ, the bone-forming osteoblasts and bone-resorbing osteoclasts form the physiological basis of bone remodeling process. During pathological process of numerous inflammatory diseases, these two aspects are uncoupled and the balance is usually tipped in favor of bone destruction. Evidence suggests that the inflammatory destruction of bone is mainly attributed to oxidative stress and is closely related to mitochondrial dysfunction. The mechanisms underlying osteogenic dysfunction in inflammation still need further investigation. Reactive oxygen species (ROS) is associated with mitochondrial dysfunction and cellular damage. Here, we reported an unexplored role of cyclophilin D (CypD), the major modulator of mitochondrial permeability transition pore (mPTP), and the CypD-mPTP axis in inflammation-induced mitochondrial dysfunction and bone damage. And the protective effects of knocking down CypD by siRNA interference or the addition of cyclosporin A (CsA), an inhibitor of CypD, were evidenced by rescued mitochondrial function and osteogenic function of osteoblast under tumor necrosis factor-alfa (TNF-alfa) treatment. These findings provide new insights into the role of CypD-mPTP-dependent mitochondrial pathway in the inflammatory bone injury. The protective effect of CsA or other moleculars affecting the mPTP formation may hold promise as a potential novel therapeutic strategy for inflammation-induced bone damage via mitochondrial pathways