Análise da Expressão Gênica Durante a Diferenciação Osteogênica de Células Mesenquimais Estromais de Medula Óssea de Pacientes Portadores de Osteogênese Imperfeita
Notice bibliographique
Résumé
Osteogenesis imperfecta (OI) is characterized as a genetic disorder in which a generalized osteopenia leads to short stature, bone fragility and serious skeletal deformities. Mesenchymal stem cells (MSCs) are precursors present in adult bone marrow that can differentiate into osteoblasts, adipocytes and myoblasts that have been given great importance as a source cell therapy. The aim of this study was to analyze the gene expression profile during osteogenic differentiation from mesenchymal stem cells from bone marrow taken from patients diagnosed with Osteogenesis Imperfecta and control subjects. Samples were collected from three normal individuals and five samples from patients with Osteogenesis Imperfecta. Mononuclear cells (MON) were isolated to obtain mesenchymal cells that were expanded until third passage when the stimulus for osteogenic differentiation was induced. Analyses were also conducted to count the CFU-F and for four of the five samples from patients with OI, the number of CFU-F observed was lower than generally found for normal samples. Cells were collected for analysis of cell immunophenotyping by flow cytometry and RNA was extracted from the resulting sample called T0. Remaining cells were stimulated for osteogenic differentiation. After a day in culture with stimulation, cells from another bottle had their RNA extracted (T1), and the same procedure was performed on days 2 (T2), 7 (T7), 12 (T12), 17 (T17) and 21 (T21). All samples have shown potential of in vitro differentiation into osteoblasts and adipocytes. Immunophenotyping of mesenchymal cells was performed and samples of all patients had immunophenotypic profile consistent with previous works. We identified mutations in COL1A1 and / or COL1A2 responsible for developing the disease for four of five patients. For the patient with Osteogenesis Imperfecta and Bruck Syndrome, coding region of the gene PLOD2 was also sequenced, but no mutations were found. The gene expression analysis was performed by microarray and identified several genes with differential expression. Some genes of fundamental importance in osteoblast differentiation showed lower expression in samples from patients with OI, suggesting a minor involvement of MSCs of patients with osteogenic lineage. Other genes also confirmed their differential expression by Real Time PCR. We observed an increased expression of genes related to adipocytes, suggesting an increased adipogenic differentiation at the expense of osteogenic differentiation. The expression of PLOD2 gene variants proved to be different between normal samples, OI and the patient with Bruck Syndrome. There was also evidence of differential expression of 29b microRNA, with established role during osteogenic differentiation, suggesting a mechanism dependent regulation of mRNA abundance of its gene target, COL1A1.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,002 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,003 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; les deux têtes enseignantes s’accordent sur ce qui est montré ici.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».