Genetic polymorphisms of the wint receptor LRP5 are differentially associated with trochanteric and cervical hip fractures

Producción CientíficaPurpose. Epidemiological studies suggest that cervical and trochanteric hip fractures have different pathogenesis. We planned to test the hypothesis that genetic factors have different influences on both types of fractures. Methods. Ten polymorphisms of genes known to play an important role in skeletal homeostasis (estrogen receptor alpha [ESR1], aromatase [CYP19A1], type I collagen [COL1A1], and lipoprotein receptor-related protein 5 [LRP5]) were analyzed in 471 Spanish patients with fragility hip fractures. Results. Two polymorphisms of the LRP5 gene (rs7116604 and rs3781600) were associated with the type of fracture (p-value 0.0085 and 0.0047, respectively). The presence of rare alleles at each locus was associated with trochanteric fractures over cervical fractures (OR 1.7 in individuals with at least one rare allele at rs7116604 or rs3781600 loci, in comparison with the common homozygotes). Considering individuals bearing the four common alleles as reference, the OR for trochanteric fractures was 1.6 in those with 1 or 2 rare alleles, and 7.5 in those with 3 or 4 rare alleles (p-value for trend 0.0074), which is consistent with an allele-dosage effect. There were no significant differences in the frequency distributions of the ESR1, CYP19A1 and COL1A1 genotypes between trochanteric and cervical fractures in either the original group or in an extended group of 818 patients. Conclusions. These results suggest LRP5 alleles influence the type of hip fractures. They support the view that different genetic factors are involved in cervical and trochanteric fractures, which should be taken into consideration in future genetic association studies

Scale of Goals of Study for University Students

Actualmente disponemos de gran cantidad de trabajos que muestran la implicación de las metas de estudio en la motivación por estudiar y aprender. Este trabajo analiza la motivación académica y, especialmente, la variable “metas de estudio”. El principal propósito de esta investigación es conocer las características psicométricas de la adaptación de la Escala de Metas de Estudio a la población universitaria chilena. Los participantes son 542 estudiantes chilenos, de distintas facultades universitarias. Los resultados del análisis factorial y de consistencia interna son aceptables en las tres subescalas. Estos resultados fundamentan el uso de la Escala de Metas de Estudio para evaluar la motivación al estudio de alumnas y alumnos universitarios en Chile (CL).At the present time we have great amount of works that show the implication of the goals of study in the motivation to study and to learn. In this paper the academic motivation and, specially, the variable “goals of study” is assess. The principal aim of the present research is know the Questionnaire to Measure Achievement Goal Tendency’s psicometric characteristics with 542 Chilean university students of different faculties. Results of the factor analysis and the internal consistency are acceptable in three subscales. In conclusion, these results support the use of the Questionnaire to Measure Achievement Goal Tendencies to assess the study motivation in university students in Chile (CL).(undefined

Internal friction associated with ε martensite in shape memory steels produced by casting route and through additive manufacturing: Influence of thermal cycling on the martensitic transformation

Among the different families of shape memory alloys (SMA), the Fe-Mn-Si-Cr-Ni alloys have attracted a renewed interest because of its low cost, high corrosion resistance and high recovery strength during the shape memory effect, and the new technologies of additive manufacturing offer unforeseen possibilities for this family of SMA. In the present work, the reversible gamma - epsilon martensitic transformation (MT), responsible for the shape memory effect, is studied in two Fe-Mn-Si-Cr-Ni alloys with high (20.2 wt%) and low (15.8 wt%) Mn content, produced by the conventional route of casting and rolling, in comparison with the MT in another similar alloy, with intermediate Mn content (19.4 wt%), which was produced by gas atomization and additive manufacturing through laser metal deposition. The forward and reverse gamma - epsilon MT is studied by mechanical spectroscopy through the internal friction spectra and the dynamic modulus variation, together with a parallel microstructural characterization including in-situ observation of the gamma - epsilon MT during cooling and heating at the scanning electron microscope. The evolution of the transformed fraction of epsilon martensite, evaluated through the integral area of the internal friction peak, was followed along thermal cycling in all three alloys. Both, the internal friction and the electron microscopy studies show that the epsilon martensite amount increases very fast during the first few cycles, and then decreases with a tendency towards its stabilization for many tens of cycles. The results show that the gamma - epsilon MT is more stable on cycling in the additive manufactured sample than in the conventionally processed samples, opening new avenues for designing shape memory steels to be specifically processed through additive manufacturing.This work was supported by the ELKARTEK-CEMAP (KK-2020/00047) project from the Industry Department of the Basque Government, and the GIU-17/071 from the University of the Basque Country, UPV/EHU. This work made use of the SGIKER facilities at the UPV/EHU

Differential analysis of genome-wide methylation and gene expression in mesenchymal stemcells of patients with fractures and osteoarthritis

Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures. We obtained hMSCs from the femoral heads of women undergoing hip replacement due to hip fractures and controls with hip osteoarthritis. DNA methylation was explored with the Infinium 450K bead array. Transcriptome analysis was done by RNA sequencing. The genomic analyses revealed that most differentially methylated loci were situated in genomic regions with enhancer activity, distant from gene bodies and promoters. These regions were associated with differentially expressed genes enriched in pathways related to hMSC growth and osteoblast differentiation. hMSCs from patients with fractures showed enhanced proliferation and upregulation of the osteogenic drivers RUNX2/OSX. Also, they showed some signs of accelerated methylation aging. When cultured in osteogenic medium, hMSCs from patients with fractures showed an impaired differentiation capacity, with reduced alkaline phosphatase activity and poor accumulation of a mineralized matrix. Our results point to 2 areas of potential interest for discovering new therapeutic targets for low bone mass disorders and bone regeneration: the mechanisms stimulating MSCs proliferation after fracture and those impairing their terminal differentiation

Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders

Producción CientíficaWe reported previously that the expression of Wnt-related genes is lower in osteoporotic hip fractures than in 26 osteoarthritis. We aimed to confirm those results by analyzing β-catenin levels and explored potential genetic 27 and epigenetic mechanisms involved. 28 β-Catenin gene expression and nuclear levelswere analyzed by real time PCR and confocal immunofluorescence. 29 Increased nuclear β-catenin was found in osteoblasts isolated from patients with osteoarthritis (99 ± 4 30 units vs. 76 ± 12, p = 0.01, n = 10), without differences in gene transcription, which is consistent with 31 a post-translational down-regulation of β-catenin and decreased Wnt pathway activity. 32 Twenty four single nucleotide polymorphisms (SNPs) of genes showing differential expression between fractures 33 and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated from blood of 853 pa- 34 tients. The genotypic frequencies were similar in both groups of patients, with no significant differences. 35 Methylation ofWnt pathway genes was analyzed in bone tissue samples (15 with fractures and 15 with osteo- 36 arthritis) by interrogating a CpG-based methylation array. Six genes showed significant methylation differences 37 between both groups of patients: FZD10, TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating 38 agent 5-deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell line, whereas it down- 39 regulated other 16 genes. 40 In conclusion,Wnt activity is reduced in patientswith hip fractures, in comparisonwith thosewith osteoarthritis. 41 It does not appear to be related to differences in the allele frequencies of the Wnt genes studied. On the other 42 hand, methylation differences between both groups could contribute to explain the differences inWnt activit

Puesta en marcha de un sistema de evaluación formativa multidisciplinar aplicado a asignaturas de Ingeniería Química y Nutrición en el Grado en Ciencia y Tecnología de los Alimentos

Ponencia presentada en: VIII Jornadas de Innovación Docente de la UBU, Burgos, 5 de abril de 2016, organizadas por el Instituto de Formación e Innovación Educativa-IFIE de la Universidad de Burgo

Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with replication

Objectives. Genes explaining the susceptibility to osteoporosis have not been fully elucidated. Our objective was to explore the association of polymorphisms capturing common variations of the lipoprotein receptor related protein (LRP) 5 and 6 genes, encoding two Wnt receptors, with femoral neck bone mineral density (BMD) and osteoporotic fractures of the spine and the hip. Design. Cross-sectional, case-control and replication genetic association study. Methods. Thirty nine tagging and functional single nucleotide polymorphisms (SNP) were analyzed in a group of 1043 postmenopausal women and 394 women with hip fractures. The results were replicated in a different group of 342 women. Results. Three SNPs of the LRP6 gene were associated with BMD (nominal uncorrected pvalues< 0.05) in the discovery cohort. One showed a significant association after multiple test correction; two of them were also associated in the replication cohort, with a combined standardized mean difference of 0.51 (p=0.009) and 0.65 (p<0.0001) across rs11054704 and rs2302685 genotypes. In the discovery cohort, several LRP5 SNPs were associated with vertebral fractures (odds ratio 0.67; p=0.01), with hip fractures (unadjusted odds ratios between 0.59 and 1.21, p=0.005-0.033, but not significant after multiple test- or age-adjustment), and with height and the projected femoral neck area, but not with BMD. Transcripts of LRP5 and LRP6 were similarly abundant in bone samples. Conclusions. In this study we found common polymorphisms of LRP5 associated with osteoporotic fractures, and polymorphisms of the LRP6 gene associated with BMD, thus suggesting them as likely candidates to contribute explaining the hereditary influence on osteoporosis

Estudio de la toxicidad aguda y subaguda oral del extracto etanólico de las hojas de Hamelia patens (Rubiceae) en ratón

The ethanol extract of leaves from Hamelia patens was evaluated for acute and sub-acute oral toxicity. The single oral doses of the ethanol extract at 5, 50, 300, and 2000 mg/kg body weight did not produce mortality or significant changes in the general behaviors. In the sub-acute toxicity study, the ethanol extract was administrated orally at a dose of 2000 mg/km/day for 28 days. The results show a CL50 up from 2000 mg/kg, which is indicative of safe use for the human being because does not represent serious alterations in the state of health of the experimental animalsEl extracto etanólico de las hojas de Hamelia patens fue evaluado para determinar la toxicidad oral aguda y subaguda en ratones de laboratorio. Las dosis de 5, 50, 300 y 2000 mg/kg de peso corporal no produjeron mortalidad ni cambios significativos en los comportamientos generales de los animales. En el estudio de toxicidad subaguda, el extracto etanólico se administró a la dosis de 2000 mg/kg de peso corporal diariamente por un período de 28 días. Los resultados muestran una CL 50 por encima de 2000 mg/kg, lo que es indicativo de un uso seguro para el ser humano en tanto que no representa alteraciones en el estado general de los animales experimentales

Risk Association of TOX3 and MMP7 Gene Polymorphisms with Sporadic Breast Cancer in Mexican Women

Breast cancer (BC) has one of the highest incidences and mortality worldwide. Single nucleotide polymorphisms (SNPs) in TOX3 rs3803662 and MMP7 rs1943779 have been associated with susceptibility to BC. In this case-control study, we evaluated the association of rs3803662 (TOX3)/rs1943779 (MMP7) SNPs with clinical features, immunohistochemical reactivity, and risk association with BC in women from northeastern Mexico. We compared 212 BC cases and 212 controls. DNA was isolated from peripheral blood to perform the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We calculated genotype frequencies, odds ratios, and 95% confidence intervals. We found that CT (Cytocine-Thymine) and TT (Thymine -Thymine) genotypes, and T alleles of TOX3 rs3803662, were associated with BC risk (p = 0.034, p = 0.011, respectively). SNP TOX3 rs3803662 was associated with positive progesterone receptors (PR) and triple-negative BC (TNBC) but not with estrogen receptor (ER) or HER2 reactivity. CT and TT genotypes (p = 0.006) and T alleles (p = 0.002) of SNP MMP7 rs1943779 were associated with risk of BC. We found that T alleles of TOX3 rs3803662 and MMP7 rs1943779 SNPs are associated with BC risk. These findings contribute to personalized medicine in Mexican women

Efectos de la administración sistémica y local de MSCs de pacientes con osteoporosis o artrosis en un modelo animal de fractura femoral

Introducción: El objetivo fue analizar la capacidad regenerativa de las MSCs en el tratamiento de fracturas. Material y métodos: Las MSCs son extraídas de pacientes con fractura de cadera osteoporótica o artrosis de cadera, sometidos a cirugía de sustitución protésica. Las MSCs cultivadas se inyectaron en un modelo animal con fractura femoral, estableciendo dos modelos experimentales en función de la vía de administración, sistémica (n=29) o local (n=30). La consolidación de la fractura se evaluó mediante micro-TC e histología. En el estudio radiológico se analizaron los parámetros Bone Volume/Tissue Volume, grado de consolidación (0-4) y número de corticales corticalizadas (0-4). El estudio histológico se valoró según la escala de Allen (1-6), Huo (1-10) y Puente Óseo (0-2). Para el análisis de los datos se emplearon los test estadísticos de Kruskal-Wallis y U de Mann Whitney. Resultados: El grado de consolidación radiológica y corticalización fue mejor con las MSCs cultivadas de pacientes con osteoporosis que de artrosis, siendo la diferencia significativa después de la administración sistémica (p=0,0302 consolidación; p=0,0243 corticalización). El grado histológico de consolidación también fue mejor con las MSCs cultivadas de pacientes con osteoporosis que de artrosis. Cuando se realiza la inyección sistémica, las diferencias fueron las siguientes: Allen, p=0,0278; Huo, p=0,0347; y Puente Óseo, p=0,0935. Después de la administración local en el foco de fractura: Allen, p=0,0764; Huo, p=0,0256; y Puente Óseo, p=0,0012. Conclusiones: En este estudio no hemos podido demostrar una mejoría de la terapia con MSCs, independientemente de su origen (osteoporosis o artrosis). Además, encontramos peores datos de consolidación en los animales que fueron tratados con MSCs cultivadas de pacientes con artrosis, particularmente si las células se inyectaron por vía intravenosa. Estas diferencias dependieron de una influencia inhibitoria que podría estar relacionada con los procesos inmunes, en el caso de las MSCs de artrosis, o el atrapamiento de las células en los tejidos viscerales, en el caso de la administración sistémica. Sin embargo, la consolidación de las fracturas con MSCs de pacientes con osteoporosis se comparó favorablemente con las MSCs de pacientes con artrosis. Por todo ello, podemos concluir que las MSCs de pacientes con osteoporosis no tienen peores capacidades de regeneración ósea que las MSCs de individuos no osteoporóticos de edad similar