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Lozano D.,Institute Investigacion Sanitaria IIS | Lozano D.,Hospital Universitario La Paz | Sanchez-Salcedo S.,Institute Investigacion Sanitaria Hospital | Sanchez-Salcedo S.,Research Center Perteneciente Red Of Bioingenieria | And 9 more authors.
Acta Biomaterialia | Year: 2014

Biopolymer-coated nanocrystalline hydroxyapatite (HA) made as macroporous foams which are degradable and flexible are promising candidates as orthopaedic implants. The C-terminal (107-111) epitope of parathyroid hormone-related protein (PTHrP) exhibits osteogenic properties. The main aim of this study was to evaluate whether PTHrP (107-111) loading into gelatin-glutaraldehyde biopolymer-coated HA (HAGlu) scaffolds would produce an optimal biomaterial for tissue engineering applications. HAGlu scaffolds with and without PTHrP (107-111) were implanted into a cavitary defect performed in both distal tibial metaphysis of adult rats. Animals were sacrificed after 4 weeks for histological, microcomputerized tomography and gene expression analysis of the callus. At this time, bone healing occurred only in the presence of PTHrP (107-111)-containing HAGlu implant, related to an increase in bone volume/tissue volume and trabecular thickness, cortical thickness and gene expression of osteocalcin and vascular cell adhesion molecule 1, but a decreased gene expression of Wnt inhibitors, SOST and dickkopf homolog 1. The autonomous osteogenic effect of the PTHrP (107-111)-loaded HAGlu scaffolds was confirmed in mouse and human osteoblastic cell cultures. Our findings demonstrate the advantage of loading PTHrP (107-111) into degradable HAGlu scaffolds for achieving an optimal biomaterial that is promising for low load bearing clinical applications. © 2014 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.

Portal-Nunez S.,Institute Investigacion Sanitaria IIS | Portal-Nunez S.,Institute Salud Carlos III ISCIII | Ardura J.A.,Institute Investigacion Sanitaria IIS | Ardura J.A.,Institute Salud Carlos III ISCIII | And 18 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2016

In the present study, the possibility that a diabetic (DM) status might worsen age-related bone deterioration was explored in mice. Male CD-1 mice aged 2 (young control group) or 16 months, nondiabetic or made diabetic by streptozotocin injections, were used. DM induced a decrease in bone volume, trabecular number, and eroded surface, and in mineral apposition and bone formation rates, but an increased trabecular separation, in L1-L3 vertebrae of aged mice. Three-point bending and reference point indentation tests showed slight changes pointing to increased frailty and brittleness in the mouse tibia of diabetic old mice. DM was related to a decreased expression of both vascular endothelial growth factor and its receptor 2, which paralleled that of femoral vasculature, and increased expression of the pro-adipogenic gene peroxisome proliferator-activated receptor γ and adipocyte number, without affecting β-catenin pathway in old mouse bone. Concomitant DM in old mice failed to affect total glutathione levels or activity of main anti-oxidative stress enzymes, although xanthine oxidase was slightly increased, in the bone marrow, but increased the senescence marker caveolin-1 gene. In conclusion, DM worsens bone alterations of aged mice, related to decreased bone turnover and bone vasculature and increased senescence, independently of the anti-oxidative stress machinery. © 2015 The Author. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

Burillo E.,Institute Investigacion Sanitaria IIS | Burillo E.,Institute Salud Carlos III | Mateo-Gallego R.,Institute Investigacion Sanitaria IIS | Mateo-Gallego R.,Institute Salud Carlos III | And 10 more authors.
Lipids in Health and Disease | Year: 2012

Background: Omega-3 poly-unsaturated fatty acids (ω-3 PUFAs) have demonstrated to be beneficial in the prevention of cardiovascular disease, however, the mechanisms by which they perform their cardiovascular protection have not been clarified. Intriguingly, some of these protective effects have also been linked to HDL. The hypothesis of this study was that ω-3 PUFAs could modify the protein cargo of HDL particle in a triglyceride non-dependent mode. The objective of the study was to compare the proteome of HDL before and after ω-3 PUFAs supplemented diet. Methods. A comparative proteomic analysis in 6 smoker subjects HDL before and after a 5weeks ω-3 PUFAs enriched diet has been performed. Results: Among the altered proteins, clusterin, paraoxonase, and apoAI were found to increase, while fibronectin, α-1-antitrypsin, complement C1r subcomponent and complement factor H decreased after diet supplementation with ω-3 PUFAs. Immunodetection assays confirmed these results. The up-regulated proteins are related to anti-oxidant, anti-inflammatory and anti-atherosclerotic properties of HDL, while the down-regulated proteins are related to regulation of complement activation and acute phase response. Conclusions: Despite the low number of subjects included in the study, our findings demonstrate that ω-3 PUFAs supplementation modifies lipoprotein containing apoAI (LpAI) proteome and suggest that these protein changes improve the functionality of the particle. © 2012 Burillo et al.

Portal-Nunez S.,Institute Investigacion Sanitaria IIS | Portal-Nunez S.,Institute Salud Carlos III | Manassra R.,Institute Salud Carlos III | Manassra R.,Complutense University of Madrid | And 9 more authors.
Age | Year: 2013

An age-related bone loss occurs, apparently associated with the concomitant increase in an oxidative stress situation. However, the underlying mechanisms of age-related osteopenia are ill defined since these studies are time consuming and require the use of many animals (mainly rodents). Here, we aimed to characterize for the first time the bone status of prematurely aging mice (PAM), which exhibit an increased oxidative stress. Tibiae from adult (6 months) PAM show an increase in bone mineral density (BMD) and bone mineral content (assessed by bone densitometry) versus those in their normal counterparts (non-prematurely aging mice, NPAM) and similarly decreased in both kinds of mouse with age. However, at this bone site, trabecular BMD (determined by μ-computerized tomography) was similar in both adult PAM and old (18 months) NPAM. Femurs from these groups of mice present an increase in oxidative stress, inflammation, osteoclastogenic, and adipogenic markers, but a decrease in the gene expression of osteoblastic differentiation markers and of the Wnt/β-catenin pathway. Our findings show that adult PAM recapitulate various age-related bone features, and thus are a suitable model for premature bone senescence studies. © 2012 American Aging Association.

Salinas A.J.,Complutense University of Madrid | Salinas A.J.,CIBER ISCIII | Esbrit P.,Institute Investigacion Sanitaria IIS | Esbrit P.,Institute Salud Carlos III | And 2 more authors.
Biomaterials Science | Year: 2013

Biomimetics takes advantage of natural strategies for the solution of technological problems, including the proper design of biomaterials. Living bone exhibits a hierarchical porosity with both giant and nanometric pores which must be reproduced for the design of biomaterials for hard tissue repair. Bioactive and degradable bioceramics are a good alternative for the manufacture of scaffolds. Tissue engineering approaches to improve bone regeneration include strategies supporting endogenous osteoblast adhesion, proliferation (osteoconduction), osteoinduction by growth factors, and osteoprogenitors. Understanding the natural ossification mechanisms and the role of biomolecules involved in this process is a requirement for the design of bone tissue scaffolds. Mesoporous bioactive ceramics, namely mesoporous silica and templated glasses with nanometric pores to host growth factors, conformed into 3D scaffolds with micrometric porosity by rapid prototyping, are a good option for bone regeneration. In this regard, biomolecules such as well characterized bone morphogenetic proteins and others under current research, such as osteostatin and osteoprogenitors, are promising strategies in bone tissue engineering applications. Future developments in biomaterials will come in both micro- and nano- scales, and molecular and cell biology approaches will provide suitable solutions to the demanding needs of these compounds. © 2013 The Royal Society of Chemistry.

Blasco-Fontecilla H.,Hospital Universitario Puerta Of Hierro | Blasco-Fontecilla H.,Research Center Biomedica En Red Of Salud Mental Cibersam | Blasco-Fontecilla H.,Autonomous University of Madrid | Gonzalez-Perez M.,Hospital Universitario Puerta Of Hierro | And 5 more authors.
Revista de Psiquiatria y Salud Mental | Year: 2016

Objective To examine the effectiveness of playing chess as a treatment option for children with ADHD. Methods Parents of 44 children ages 6 to 17 with a primary diagnosis of ADHD consented to take part in the study. Parents completed the Spanish version of the Swanson, Nolan and Pelham Scale for parents (SNAP-IV) and the Abbreviated Conner's Rating Scales for parents (CPRS-HI) prior to an 11-week chess-training program. We used a paired t-test to compare pre- and post-intervention outcomes, and Cohen-d calculations to measure the magnitude of the effect. The statistical significance was set at P <.05. Results Children with ADHD improved in both the SNAP-IV (t = 6.23; degrees of freedom (df) = 41; P <.001) and the CPRS-HI (t = 5.39; df = 33; P <.001). Our results suggest a large effect in decreasing the severity of ADHD as measured by the SNAP-IV (d = 0.85) and the CPRS-HI (d = 0.85). Furthermore, we found a correlation between intelligence quotient and SNAP-IV improvement (P <.05). Conclusions The results of our pilot study should be interpreted with caution. This pilot project highlights the importance of carrying out larger studies with a case-control design. If our results are replicated in better designed studies, playing chess could be included within the multimodal treatment of ADHD. © 2014 SEP y SEPB.

Esbrit P.,Institute Investigacion Sanitaria IIS | Esbrit P.,Institute Salud Carlos III | Alcaraz M.J.,Institute Salud Carlos III | Alcaraz M.J.,University of Valencia
Biochemical Pharmacology | Year: 2013

Osteoporosis is characterized by low bone mineral density and/or poor bone microarchitecture leading to an increased risk of fractures. The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption. Osteoporosis therapies have mostly relied on antiresorptive drugs. An alternative therapeutic approach for osteoporosis is currently available, based on the intermittent administration of parathyroid hormone (PTH). Bone anabolism caused by PTH therapy is mainly accounted for by the ability of PTH to increase osteoblastogenesis and osteoblast survival. PTH and PTH-related protein (PTHrP)-an abundant local factor in bone- interact with the common PTH type 1 receptor with similar affinities in osteoblasts. Studies mainly in osteoporosis rodent models and limited data in postmenopausal women suggest that N-terminal PTHrP peptides might be considered a promising bone anabolic therapy. In addition, putative osteogenic actions of PTHrP might be ascribed not only to its N-terminal domain but also to its PTH-unrelated C-terminal region. In this review, we discuss the underlying cellular and molecular mechanisms of the anabolic actions of PTH and the similar potential of PTH-related protein (PTHrP) to increase bone mass and improve bone regeneration. © 2013 Elsevier Inc. All rights reserved.

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