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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

Dental maturation of the permanent mandibular teeth of South African children and the relation to chronological age

Phillips, Vincent Michael January 2009 (has links)
Philosophiae Doctor - PhD / Age estimation of the skeletal remains of children can be accomplished by examination of the ossification centres and the fusion of the epiphyseal plates of long bones. Dental age estimation is done by examining the eruption of the deciduous and permanent teeth. Both these methods are inaccurate and are subject to the nutritional status of the individual. A more accurate method of age estimation is by the examination of radiographic images of the developmental stages of the tooth crown and root formation. Two methods of dental age estimation used are those of Moorrees, Fanning and Hunt (1963) (MFH) and that of Demirjian, Goldstein and Tanner (1973) (DGT). These methods were tested on a sample of 913 Tygerberg dental patients; a random mixture of Caucasoid and Khoisanoid children. The MFH method under-estimated the ages of the sample by an average of 0.91 years and the DGT method over-estimated the ages by an average of 0.89 years. Samples of Indian and Negroid children from Kwa-Zulu Natal were tested in a similar manner and the results showed similar under and over-estimation of the ages by these methods. The Negroid children were labelled the Zulu sample. Correction factors were derived for the MFH and DGT methods of dental age estimation when used on Tygerberg, Indian and Zulu children. These correction factors were tested on the samples and found to improve the accuracy of the age estimation methods of MFH and DGT significantly.A second sample group of Tygerberg, Indian and Zulu children were then tested firstly using the standard method of MFH and DGT and the using the correction factors. The results showed that the correction factors improved the age estimation on these samples except in the case of the DGT method on Zulu children. A sample of Xhosa speaking children were added to the two Zulu samples and made an Nguni sample. The Tygerberg samples were combined as were the Indian samples to form data bases for the construction of dental age related tables for Tygerberg, Indian and Nguni children. These tables show that there are distinct differences in the ages at which the teeth develop in the different sample groups and that dental age related tables are necessary for children of different population origins. Statistical analysis of the age related tables from this study (Phillips Tables) show these tables are more accurate in the age estimation of South African children.
62

Estudo dos efeitos da irradiação pulsada de baixa intensidade sobre o desenvolvimento de segmentos de coluna vertebral implantados em camundongos isogênicos / Low-intensity pulsed ultrasonic irradiation effects on development of vertebral column segments implanted in isogenics mice

Andrezza Furquim da Cruz 15 April 2005 (has links)
Estudo dos efeitos da irradiação ultra-sônica pulsada de baixa intensidade sobre o desenvolvimento de segmentos da coluna vertebral implantados em camundongos isogênicos / The aim of the present research was evaluate the action of low-intensity pulsed ultrasonic irradiation on development and ossification of vertebral column blastemas, through mice new born tail segments implants in adult receptor isogenic mice lineages C57BL/6 and Balb/C. New born tail segments were implanted in subcutaneous tissues of adults isogenics mice C57BL/6 and intramuscularly in adults isogenics mice Balb/C. After 24 hours the implant, the animals in both groups, were stimulated with the low-intensity pulsed ultrasound (LIPUS), 10 minutes per day. After 5 days of stimulus, the receptors animals were death and had the implanted tails removed for histopathology, trhrough Periodic Acid Schiff plus Alcian Blue (PAS/AB), Masson's tricomico and hem lumen-eosin (HE). The group of animals stimulated which received subcutaneous implant presented the implant with accelerated in inter-vertebral diks, faces to chondrocytes organization and chondroblastes findings in cartilaginous matrix, showing maturity in fiber cartilages arrangements. It was observed too, a collagen fibers enlargement in the disks fibro cartilage which show more dense next the pulposo nucleus in the segments implanted and stimulated, compared with the controls segments. The areas of the segments were available by Fisher's test and Student's t. It didn't watch significant differences in the vertebral bodies' areas sizes in the animals which implant was subcutaneous (p'< OU = '0.05). In the intramuscular implants animals group, it was observed a major velocity in the hialuronic acid matrix formation in the intervertebral disks after LIPUS stimulus. Moreover, the fibrous ring fiber cartilages' were better organized with large number of cells inside the cartilaginous matrix compared with the controls segments. With regard to the vertebral bodies in the intramuscular implants, it's not verifies significant increases in the areas (p'< OU =' 0,05). The findings allow conclude that LIPUS should promote the ontogenetic differentation of the structural components of the mice vertebral column more quickly, trhough vertebras endochondral ossification microscopic evaluation and the inter-vertebral disks components differentiation, follow the methodology employed.
63

Evaluación de la osificación de la sutura media palatina y la discrepancia transversal maxilar en pacientes de 18 a 40 años de un centro radiológico de Lima - Perú

Escudero Tacusi-Oblitas, Fresia Narda, Quiquinlla Asto, Deybbit Jordy 09 July 2019 (has links)
Objetivo: Evaluación de la osificación de la sutura media palatina y la discrepancia transversal maxilar en pacientes de 18 a 40 años de un centro radiológico de Lima - Perú. Materiales y métodos: Se realizó un estudio observacional de corte transversal. La muestra estuvo constituída por 234 tomografías computarizadas de haz cónico en pacientes de 18 a 40 años de edad, donde se realizó el análisis de Penn CBCT para la evaluación de la discrepancia transversal maxilar mientras que la clasificación de Angelieri se utilizó para evaluar la osificación de la sutura media palatina. Se utilizaron las pruebas de Chi cuadrado, U Mann Whitney y Correlación de Spearman para evaluar si existe relación entre las variables de estudio. Resultados: La discrepancia transversal fue de 7.27mm. Por otro lado, se encontró que en el rango de 18 a 28 años de edad prevalece el estado B con 65 pacientes, mientras que en el rango de 29 a 40 años hubieron 50 pacientes del mismo estado. Así mismo, existe asociación entre la discrepancia transversal maxilar con el género, mientras que la osificación de la sutura media palatina no está relacionada al género. Conclusiones: Se concluye que no se encontró una asociación entre la osificación de la sutura media palatina, la discrepancia transversal y la edad, esto indica que cada variable es independiente. Por otro lado, existe asociación entre la discrepancia transversal maxilar y el género. / Objective: Evaluation of the ossification of the mid-palatal suture and the maxillary transverse discrepancy in patients aged 18 to 40 years from a radiological center in Lima-Peru. Materials and methods: An observational cross-sectional study was conducted. The sample consisted of 234 conical beam CT scans in patients aged 18 to 40 years, where the CBCT Penn analysis was performed for the evaluation of the maxillary transverse discrepancy, while the Angelieri classification was used to evaluate the ossification of the mid palatal suture. Chi Square, Mann–Whitney U, and Spearman Correlation tests were used to assess whether there was a relationship between the study variables. Results: The transverse discrepancy was 7.27 mm. On the other hand, it was found that in the range of 18 to 28 years of age, state B prevails with 65 patients, while in the range of 29 to 40 years there were 50 patients of the same state. Likewise, there was an association between the maxillary transverse discrepancy with the gender, while the ossification of the mid-palatal suture was not related with the gender. Conclusions: It was concluded that no association was found between the ossification of the mid-palatal suture, the transverse discrepancy, and age; this indicates that each variable is independent. On the other hand, there was an association between maxillary transversal discrepancy and gender. / Tesis
64

Using macrophages derived from human induced pluripotent stem cells to identify activators of inflammation in fibrodysplasia ossificans progressiva

Lepinski, Abigail 07 June 2020 (has links)
BACKGROUND: Inflammation is a key regulator in skeletal homeostasis during normal growth and tissue repair. However, the role that inflammation plays in skeletal processes is not well understood. Previous studies showed that damage associated molecular pattern (DAMP) molecules released after injury may contribute to immune activation and subsequent fibrosis. OBJECTIVE: This project aims to elucidate the link between tissue damage caused by trauma and the subsequent inflammatory response in a genetic condition of bone morphogenetic protein (BMP) pathway over activation. METHODS: We investigated this potential link by examining immune cells from patients with fibrodysplasia ossificans progressiva (FOP), a genetic condition of endochondral heterotopic ossification caused by activating mutations in the Activin A type I receptor (ACVR1). Patients with FOP show sensitivity to trauma, elevated serum cytokines and abnormal cytokine/chemokine secretion from monocytes and macrophages when stimulated with lipopolysaccharide in vitro. This suggested that BMP pathway activation may alter immune responses in patients with FOP. We studied macrophages derived from peripheral blood monocytes or created from human induced pluripotent stem cells (iPSC) from FOP and control subjects. Macrophages were evaluated by gene expression and culture media by multiplex cytokine analysis after stimulation with key DAMPs that were previously identified to be released after tissue injury. These DAMPs act as endogenous activators of inflammation. RESULTS: Monocyte derived macrophages from control subjects showed increased expression of pro-inflammatory cytokines in response to stimulation with DAMPs, HMGB1 and S100A8/A9. FOP monocyte-derived macrophages treated with each DAMP showed elevated production of CCL22, IL-8, CCL3, and CCL8 when compared to control macrophages. However, both control and FOP macrophages showed increased production of pro-inflammatory cytokines in response to DAMPs compared to non-stimulated conditions. RNA expression profiles of FOP iPSC derived macrophages did not show significantly increased responsiveness to DAMPs compared to control. Surprisingly, control patient iPSC derived macrophages show elevated expression of TNF-a and IL-1B CONCLUSIONS: Macrophages derived from peripheral blood monocytes show that DAMPs may be responsible for macrophage activation and the development of inflammatory complications in patients with FOP. Control iPSC derived macrophages showed similarity to monocyte derived macrophages in their response to DAMPs, suggesting that our iPSC derived macrophages are an applicable model for investigating the human immune system. The dissimilarity in FOP macrophage responsiveness to endogenous activators of our two macrophage models, suggest that iPSC derived macrophages may be affected by the different differentiation and polarization methods, and needs to be characterized further. Similarly, RNA expression profiles may not reflect cytokine production patterns of stimulated iPSC macrophages and warrants further studies. / 2021-06-07T00:00:00Z
65

Bone growth following demineralized bone matrix implantation requires angiogenesis

Lam, Stephanie 22 January 2016 (has links)
Angiogenesis is required for endochondral ossification during development and fracture healing; however the exact mechanisms and temporal relationship between the two processes remains unclear. In this study, we utilize an in vivo model of endochondral ossification in mice by implanting demineralized bone matrix (DBM) proximal to the femur to induce ectopic bone formation. TNP-470, a drug known to be anti-angiogenic, was used to inhibit vascularization during the time course of de novo bone formation in order to define the role of angiogenesis during the chondrogenic phase of endochondral bone formation. Day 2, day 8, and day 16 post-surgery were selected time points to represent pre-chondrogenic, chondrogenic, and bone mineralization stages, respectively. Plain x-ray and micro-CT analysis showed that inhibition of angiogenesis led to decreased mineralized tissue formation. Inhibited angiogenesis was confirmed with qRT-PCR. Most striking, however, is that while stem cells are recruited and committed to the chondrogenic lineage, subsequent chondrogenesis failed to progress based on the failure of Sox5 and Sox6 expression, which directs chondrocyte commitment. This expands the role for angiogenesis to a much earlier stage than currently thought and places the necessity of angiogenesis very early in the endochondral ossification process.
66

Characterization of a Novel Nuclear Variant of Bmp2 and Coordinate Regulation of Col11a2 and Col27a1 by the Transcription Factor Lc-Maf

Mayo, Jaime Lynn 13 July 2007 (has links) (PDF)
ABSTRACT I CHARACTERIZATION OF A NOVEL NUCLEAR VARIANT OF BMP2Bone morphogenetic protein 2 (Bmp2) is a signaling protein that was first detected by its ability to induce cartilage and bone formation. It has since been implicated in broad variety of developmental, patterning, and disease processes. To date, Bmp2 has only been known to function as an extracellular signaling molecule. However, we have obtained clear evidence for a nuclear form of Bmp2. This nuclear variant, nBmp2, contains a bipartite NLS that overlaps the site of proteolytic cleavage. The NLS remains intact and functional when translation of Bmp2 initiates from a downstream alternative start codon. The resulting protein lacks the signal peptide and is therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing and secretion. Instead, the uncleaved protein containing the intact NLS is translocated to the nucleus. Preliminary functional analyses in zebrafish indicate that nBmp2 is critical for proper heart development. To determine if this function is conserved in mammals, we have also generated mice harboring a null allele for nBmp2. ABSTRACT II COORDINATE REGULATION OF COL11A2 AND COL27A1 BY THE TRANSCRIPTION FACTOR LC-MAF During skeletal development, long bones of the body develop from a cartilage template that is progressively replaced by bone. This process of endochondral ossification requires precisely coordinated expression of extracellular matrix proteins such as the cartilage-specific collagens. In this study, enhancer/reporter assays demonstrated that the transcription factor Lc-Maf inhibits the transcriptional activity of a cartilage-specific Col11a2 enhancer element while a cartilage-specific COL27A1 enhancer element was strongly activated by Lc-Maf. Site-directed mutagenesis identified the binding region within the COL27A1 enhancer, and it was found to be unlike any known consensus Maf family binding site. The in vivo significance of these results was examined using immunohistochemistry and in situ hybridization in mouse limbs undergoing endochondral ossification. Taken together, these results suggest that Lc-Maf participates in the developmental transition from proliferating to hypertrophic chondrocytes during endochondral ossification by coordinately downregulating Col11a2 and upregulating Col27a1 collagen gene expression.
67

Collagen X is dispensable for hypertrophic differentiation and endochondral ossification of human iPSC-derived chondrocytes / X型コラーゲンはヒトiPS細胞由来軟骨細胞の肥大化および内軟骨性骨化に必須ではない

Kamakura, Takeshi 24 July 2023 (has links)
京都大学 / 新制・課程博士 / 博士(医科学) / 甲第24843号 / 医科博第151号 / 新制||医科||10(附属図書館) / 京都大学大学院医学研究科医科学専攻 / (主査)教授 齋藤, 潤, 教授 遊佐, 宏介, 教授 松田, 秀一 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
68

Micro-engineered substrates as bone extracellular matrix mimics

Bilem, Ibrahim 24 April 2018 (has links)
Il est de plus en plus évident que la matrice extracellulaire (MEC), au-delà de sa fonction d’échafaudage cellulaire, génère des signaux de nature biochimique et biophysique jouant un rôle primordial au cours du processus de différenciation des cellules souches. A l’heure actuelle, plus de 15 différents facteurs extrinsèques (environnementaux), incluant l’organisation spatiale de la MEC, sa topographie, rigidité, porosité, biodégradabilité et chimie ont été identifiés comme modulateurs potentiels de la différenciation des cellules souches en lignées cellulaires spécialisées. Ainsi, il est plausible que l’intégration d’un biomatériau au sein de l’organisme dépendra largement de sa capacité à mimer les propriétés de la MEC du tissu à remplacer. Récemment, les techniques de micro-ingénierie ont émergé comme outil innovant pour découpler les différentes propriétés de la MEC et étudier l’impact individuel ou combiné de ces facteurs sur le comportement des cellules souches. De plus, ces techniques de microfabrication ont un intérêt particulier dans une perspective de reconstruction de la MEC dans tous ses aspects, in vitro. Dans ce projet de thèse, le concept de déconstruction/reconstruction de la complexité de la MEC a été appliqué pour récapituler, in vitro, plusieurs aspects inhérents à la MEC osseuse et explorer leurs effets individuels ou combinés sur la différenciation ostéoblastique des cellules souches mésenchymateuses (CSMs) humaines. Trois principales composantes ont été utilisées tout au long du projet : un matériau modèle (verre borosilicate), des séquences peptidiques mimétiques dérivées de la MEC naturelle, favorisant à la fois l’adhérence cellulaire (peptide RGD) et la différenciation ostéoblastique (peptide BMP-2) des CSMs prélevées de la moelle osseuse des patients. La première étude du projet consiste à greffer, d’une manière aléatoire, les peptides RGD et/ou BMP-2 sur la surface du matériau. Brièvement, nous avons développé trois types de matériaux bioactifs : matériaux fonctionnalisés avec le peptide RGD, matériaux fonctionnalisés avec le peptide BMP-2 et matériaux bi-fonctionnalisés avec les peptides RGD/BMP-2. La caractérisation physicochimique de ces matériaux a été réalisée en utilisant la spectrométrie photoélectrique à rayons X (XPS) pour évaluer la composition chimique de la surface, la microscopie à force atomique (AFM) pour évaluer la topographie de la surface et la microscopie à fluorescence pour confirmer la présence des peptides sur la surface et évaluer leur densité. L’objectif de cette étude est d’évaluer le potentiel individuel et synergétique de ces peptides à induire et contrôler la différentiation ostéoblastique des CSMs. Dans un premier temps, la caractérisation physicochimique nous a permis de confirmer l’immobilisation covalente des peptides sur la surface et de mesurer leur densité. En effet, la densité des peptides, mesurée sur les surfaces greffées uniquement avec le peptide RGD ou BMP-2, était de 1.8 ± 0.2 pmol/mm² et 2.2 ± 0.3 pmol/mm², respectivement. Cependant, sur les surfaces bifonctionnalisées, la densité de chaque peptide a diminué de presque la moitié, atteignant 0.7 ± 0.1 pmol/mm² pour le peptide RGD et 1 ± 0.1 pmol/mm² pour le peptide BMP-2. Ensuite, l’évaluation biologique des différents matériaux fonctionnalisés a clairement révélé que contrairement au peptide RGD, le peptide BMP-2 induit la différenciation ostéoblastique des CSMs. Cependant, le greffage simultané des peptides RGD/BMP-2 améliore significativement la différenciation des CSMs en ostéoblastes et cela malgré la diminution significative de la densité de chaque peptide sur les surfaces bi-fonctionnalisées, comparativement aux surfaces contenant qu’un seul peptide. Ces résultats montrent que les peptides RGD et BMP-2 peuvent engendrer un effet synergétique pour améliorer la différenciation ostéoblastique des CSMs. Le second chapitre de thèse vise à déterminer si la microstructuration de la surface des matériaux avec des ligands bioactifs améliore la différenciation ostéoblastique des CSMs. En effet, les peptides RGD et BMP-2 ont été greffés séparément sur la surface du matériau sous forme de micro-motifs de différentes formes mais de taille similaire. En se basant sur des précédents travaux de littérature – discutés dans le chapitre II – nous avons sélectionné trois différentes formes de motifs peptidiques (triangle, carré et rectangle) dont la surface est de 50 μm². Ces micromotifs ont été créées grâce à une technique assez répondue et facile à utiliser qui est la photolithographie. Les surfaces microstructurées ont été caractérisées avec l’interférométrie optique et la microscopie à fluorescence. Les résultats montrent que les micromotifs peptidiques ont à la fois la forme et les dimensions prédéfinies. In vitro, les résultats de différenciation cellulaire ont révélé que la distribution spatiale des ligands à l’échelle micrométrique joue un rôle très important dans l’engagement et la différenciation des CSMs en ostéoblastes. En effet, contrairement aux micromotifs peptidiques en forme de rectangles, les micromotifs triangulaires et carrés améliorent significativement l’expression des marqueurs ostéogéniques (Runx-2 et Ostéopontine) comparativement à la distribution aléatoire des peptides. Il est important de noter que ce profile d’expression des marqueurs biologiques a été observé que sur les matériaux fonctionnalisés avec le peptide BMP-2, tant dis que les matériaux fonctionnalisés avec le peptide RGD n’ont induit aucun effet spécifique sur la différenciation des CSMs et cela peu importe la forme des micromotifs peptidiques. En conclusion, cette étude a permis d’identifier un nouveau facteur extracellulaire capable de contrôler la différenciation des CSMs. De plus, nous avons démontré que la distribution spatiale des ligands à l’échelle micrométrique affecte le devenir des CSMs, dépendamment de la nature du principe actif. Finalement, la troisième étude de ce projet de thèse est une suite logique de l’étude 1 et 2, puisqu’elle consiste à greffer simultanément les peptides RGD et BMP-2 sous forme de micromotifs. En effet, ces surfaces ont été développées afin de bénéficier à la fois de l’effet synergétique des peptides RGD/BMP-2, observé dans l’étude 1 (facteur 1), et de l’effet de la distribution spatiale contrôlée des ligands, observé dans l’étude 2 (facteur 2). Les différents types de matériaux ont été caractérisés avec les mêmes techniques de caractérisation de surface mentionnées dans l’étude 2. Les résultats montrent clairement que les surfaces microstructurées sont très bien définies et correspondent à un damier de micromotifs RGD, intercalé par un damier de micromotifs BMP-2. L’évaluation de la différenciation des CSMs sur ces matériaux a révélé que la combinaison des facteurs 1 et 2 améliore significativement la différenciation des CSMs vers le lignage ostéoblastique, comparativement à l’exposition des CSMs à un seul facteur extracellulaire (1 ou 2). De plus, cette étude confirme les résultats obtenus dans l’étude 2, puisque les micromotifs triangulaires et carrés ont permis une meilleure différenciation cellulaire, comparativement aux micromotifs rectangulaires. Il est important de noter également que l’évaluation biologique des différentes surfaces biomimétiques a été réalisée dans un milieu de culture basal qui ne contient pas de facteurs ostéogéniques solubles, afin d’étudier d’une manière assez précise et fiable les interactions des CSMs avec les différents microenvironnements in vitro développés dans ce projet. En conclusion générale, les travaux effectués jusqu’à présent ont permis d’identifier deux aspects de la MEC qui influencent considérablement la différenciation ostéoblastique des CSMs. De plus, nous avons démontré que ces deux facteurs peuvent coopérer pour induire une meilleure différenciation cellulaire. Cela révèle clairement l’intérêt des techniques de micro-ingénierie pour une meilleure et plus profonde compréhension des mécanismes d’interactions des cellules souches avec leurs niches, ce qui permettra éventuellement de concevoir des produits d’ingénierie tissulaire sur-mesure. Mots clés : Microstructuration de la surface des matériaux, matrice extracellulaire biomimétique, peptides mimétiques, BMP-2, cellules souches, ostéogenèse. / It is becoming increasingly appreciated that the role of extracellular matrix (ECM) extends beyond acting as scaffolds to providing biochemical and biophysical cues, which are critically important in regulating stem cell self-renewal and differentiation. To date, more than 15 different extrinsic (environmental) factors, including the matrix spatial organization, topography, stiffness, porosity, biodegradability and chemistry have been identified as potent regulators of stem cells specification into lineage-specific progenies. Thus, it is plausible that the behavior of biomaterials inside the human body will depend to a large extent on their ability to mimic ECM properties of the tissue to be replaced. Recently, nano- and microengineering methods have emerged as an innovative tool to dissect the individual role of ECM features and understand how each element regulates stem cell fate. In addition, such tools are believed to be useful in reconstructing complex tissue-like structures resembling the native ECM to better predict and control cellular functions. In the thesis project presented here, the concept of deconstructing and reconstructing the ECM complexity was applied to reproduce several aspects inherent to the bone ECM and harness their individual or combinatorial effect on directing human mesenchymal stem cells (hMSCs) differentiation towards the osteoblastic lineage. Three main components were used throughout this project: a model material (borosilicate glass), ECM derived peptides (adhesive RGD and osteoinductive BMP-2 mimetic peptides) and bone marrow derived hMSCs. All cell differentiation experiments were performed in the absence of soluble osteogenic factors in the medium in order to precisely assess the interplay between hMSCs and the different artificial matrices developed in the current study. First, RGD and/or BMP-2 peptides were covalently immobilized and randomly distributed on glass surfaces. The objective here was to investigate the effect of each peptide as well as their combination on regulating hMSCs osteogenic differentiation. The most important funding was that RGD and BMP-2 peptides can act synergistically to enhance hMSCs osteogenesis. Then, micropatterning technique (photolithography) was introduced to control the spatial distribution of RGD and BMP-2 at the micrometer scale. The peptides were grafted individually onto glass substrates, as specific micropatterns of varied shapes (triangular, square and rectangle geometries) but constant size (50 μm² per pattern). In this second part of the project, the focus was made on investigating the role of ligands presentation in a spatially controlled manner in directing hMSCs differentiation into osteoblasts. Herein, we demonstrated that the effect of microscale geometric cues on stem cell differentiation is peptide dependent. Finally, glass surfaces modified with combined and spatially distributed peptides were used as in vitro cell culture models to evaluate the interplay between RGD/BMP-2 crosstalk and microscale geometric cues in regulating stem cell fate. In this study, we revealed that the combination of several ECM cues (ligand crosstalk and geometric cues), instead of the action of individual cues further enhances hMSCs osteogenesis. Overall, our findings provide new insights into the role of single ECM features as well their cooperation in regulating hMSCs fate. Such studies would allow the reconstruction of stem cell microenvironment in all the aspects ex vivo, which may pave the way towards the development of clinically relevant tissue-engineered constructs. Keywords: Chemical micropatterning, bioactive surfaces, mimetic peptides, BMP-2, mesenchymal stem cells, stem-cell differentiation, stem-cell niche, osteogenesis.
69

The role of PPARgamma in cartilage growth and development using cartilage-specific PPARgamma knockout mice

Monemdjou, Roxana 07 1900 (has links)
Le cartilage est un tissu conjonctif composé d’une seule sorte de cellule nommée chondrocytes. Ce tissu offre une fondation pour la formation des os. Les os longs se développent par l'ossification endochondral. Ce processus implique la coordination entre la prolifération, la différenciation et l'apoptose des chondrocytes, et résulte au remplacement du cartilage par l'os. Des anomalies au niveau du squelette et des défauts liés à l’âge tels que l’arthrose (OA) apparaissent lorsqu’il y a une perturbation dans l’équilibre du processus de développement. À ce jour, les mécanismes exacts contrôlant la fonction et le comportement des chondrocytes pendant la croissance et le développement du cartilage sont inconnus. Le récepteur activateur de la prolifération des peroxysomes (PPAR) gamma est un facteur de transcription impliqué dans l'homéostasie des lipides. Plus récemment, son implication a aussi été suggérée dans l'homéostasie osseuse. Cependant, le rôle de PPARγ in vivo dans la croissance et le développement du cartilage est inconnu. Donc, pour la première fois, cette étude examine le rôle spécifique de PPARγ in vivo dans la croissance et le développement du cartilage. Les souris utilisées pour l’étude avaient une délétion conditionnelle au cartilage du gène PPARγ. Ces dernières ont été générées en employant le système LoxP/Cre. Les analyses des souris ayant une délétion au PPARγ aux stades embryonnaire et adulte démontrent une réduction de la croissance des os longs, une diminution des dépôts de calcium dans l’os, de la densité osseuse et de la vascularisation, un délai dans l’ossification primaire et secondaire, une diminution cellulaire, une perte d’organisation colonnaire et une diminution des zones hypertrophiques, une désorganisation des plaques de croissance et des chondrocytes déformés. De plus, la prolifération et la différenciation des chondrocytes sont anormales. Les chondrocytes et les explants isolés du cartilage mutant démontrent une expression réduite du facteur de croissance endothélial vasculaire (VEGF)-A et des éléments de production de la matrice extracellulaire. Une augmentation de l’expression de la métalloprotéinase matricielle (MMP)-13 est aussi observée. Dans les souris âgées ayant une délétion au PPARγ, y est aussi noté des phénotypes qui ressemblent à ceux de l’OA tel que la dégradation du cartilage et l'inflammation de la membrane synoviale, ainsi qu’une augmentation de l’expression de MMP-13 et des néoépitopes générés par les MMPs. Nos résultats démontrent que le PPARγ est nécessaire pour le développement et l’homéostasie du squelette. PPARγ est un régulateur essentiel pour la physiologie du cartilage durant les stades de croissance, de développement et de vieillissement. / Cartilage, a connective tissue composed of chondrocytes, provides an intermediate template on which bones are formed. Long bones develop through endochondral ossification, involving coordination between chondrocyte proliferation, differentiation and apoptosis, resulting in bone replacing cartilage. Disturbances in this balance results in skeletal abnormalities, and age-related defects including osteoarthritis (OA). The exact mechanisms that control chondrocyte function and behaviour during growth and development are unknown. Peroxisome proliferator-activated receptor (PPAR) gamma, a transcription factor involved in lipid homeostasis, has recently been suggested to be involved in bone homeostasis. However, PPARγ’s role in cartilage growth and development in vivo is unknown. Therefore, for the first time, this study examines PPARγ’s specific in vivo role in cartilage growth and development using cartilage-specific PPARγ knockout (KO) mice. Conditional KO mice were generated using LoxP/Cre system. Histomorphometric analyses of embryonic and adult mutant mice demonstrate reduced long bone growth, calcium deposition, bone density, vascularity, and delayed primary and secondary ossification. Mutant growth plates are disorganized with abnormal chondrocyte shape, proliferation and differentiation, reduced cellularity, loss of columnar organization, and shorter hypertrophic zones. Isolated mutant chondrocytes and cartilage explants show decreased vascular endothelial growth factor (VEGF)-A and extracellular matrix (ECM) production product expression, and increased matrix metalloproteinase (MMP)-13 expression. Aged mutant mice exhibit accelerated OA-like phenotypes, and enhanced cartilage degradation, synovial inflammation, MMP-13 and MMP-generated neoepitope expression. Our data demonstrate that PPARγ is required for normal skeletal development and homeostasis, and is a critical regulator of cartilage health and physiology in early growth and development and aging.
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The behaviour of trace elements during the volcanic ash-liquid interaction : example of marine and human systems / Le comportement des éléments traces lors de l'interaction de cendres volcaniques-liquide : exemple des systèmes marins et l'homme

Randazzo, Loredana Antonella 15 April 2011 (has links)
Les processus d’interaction solide-liquide régulent les mécanismes qui régissent la disponibilité des oligo-éléments en phase liquide. Dans cet article, ces processus ont été étudiés grâce à l'utilisation des éléments de terres rares (REE), car ils sont d'excellents traceurs des processus géochimiques. Le but de la première partie de ce travail était d'étudier la réactivité des particules volcaniques lors de l'interaction avec l'eau de la mer synthétique. Les résultats montrent que en dehors de la dissolution, qui est le processus principal, un procédé d'adsorption de surface se produit également, probablement sur la surface des cristaux nouvellement formé. La présence supposée de ces minéraux est suggéré par la variation temporelle de l'Y/Ho, des observations SEM et analyse XRD. Enfin, l'ajout des ligand dissous ne pas augmenter le taux de dissolution des particules volcaniques, mais modifiant la distribution de REE en phase liquide. Dans la deuxième partie de ce travail, l'étude des terres rares a été appliquée à un système humain. Ces éléments ont été utilisés, en fait, d'enquêter sur les fluides du poumon (BAL) chez les personnes exposées aux retombées de cendres volcaniques. Le résultat suggère que la co-précipitation du YLn-phosphates se produisent dans les poumons, à la suite de l'inhalation de particules volcaniques. Ce processus est confirmé par des simulations thermodynamiques et cinétiques indiquant que la cristallisation de YLn-phosphates et d'autres phases authigènes apparaît comme la conséquence de la dissolution de la fraction solubles de cendres / The solid-liquid interaction processes regulate the mechanisms governing the availability of trace elements in liquid phase. In this paper, these processes have been studied through the use of the Rare Earth Elements (REE) since they are excellent tracers of geochemical processes. The purpose of the first part of this work was to study the reactivity of volcanic particulates during the interaction with synthetic seawater. The results show that apart from the dissolution, which is the main process, a surface adsorption process also occurs, probably on the surface of newly formed crystals. The supposed presence of these minerals is suggested by the temporal variation of the Y/Ho ratio, by SEM observations and XRD analysis. Finally the addition of ligand species to dissolved media does not increase dissolution rate of volcanic particles but modify the YLn distribution in liquid phase. In the second part of this work, the Rare Earth study was applied to a human system. These elements were used, in fact, to investigate the effects due to the interactions between the inhaled atmospheric particulate matter and the lung fluids (BAL), in people exposed to fallout of volcanic ash. The results suggest that YLn-phosphate co-precipitation occurs in lungs as a consequence of inhalation of volcanic particles and their interactions with lung fluids. This process is confirmed by thermodynamic and kinetic simulations indicating that crystallisation of YLn-phosphates and other authigenic phases occurs as a consequence of the soluble ash fraction dissolution. The combination of YLn fractionation in bronchial fluids can represent a potential tracer of exposure to atmospheric fallout

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