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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(7): 1227-1235, 2024 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-39051068

RESUMO

OBJECTIVE: To investigate the role of high-mobility group AT-hook 2 (HMGA2) in osteogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs) and the effect of Hmga2 knockdown for promoting bone defect repair. METHODS: Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs. The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2. Primary mouse ADSCs (mADSCs) were transfected with Hmga2 siRNA, and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining. The expressions of osteogenic markers Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcein (OCN) in the transfected cells were detected using RT-qPCR and Western blotting. In a mouse model of critical-sized calvarial defects, mADSCs with Hmga2-knockdown were transplanted into the defect, and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining. RESULTS: GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs. Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7, CDH1, CDH2, SNAI1, SMAD9, IGF2BP3, and ALDH1A1. In mADSCs, Hmga2 knockdown significantly upregulated the expressions of RUNX2, OPN, and OCN and increased cellular alkaline phosphatase activity and calcium deposition. In a critical-sized calvarial defect model, transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation. CONCLUSION: HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs, and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.


Assuntos
Diferenciação Celular , Proteína HMGA2 , Células-Tronco Mesenquimais , Osteogênese , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , Camundongos , Tecido Adiposo/citologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , RNA Interferente Pequeno/genética , Técnicas de Silenciamento de Genes , Adipogenia/genética
2.
Genet Mol Res ; 13(1): 768-81, 2014 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-24615041

RESUMO

The Japanese eel population has dramatically declined since the 1970s. In order to conserve this species, the background genetic structure affecting these populations should be well documented. Previous genetic studies of this species have produced seemingly conflicting results, ranging from no detectable heterogeneity to small, but statistically significant variance. This study investigates the population structure of Japanese glass eels collected from 10 localities in China in 2009 using a mitochondrial DNA (mtDNA) control region and 19 polymorphic microsatellite loci. Results revealed evidence of low genetic differentiation using both mtDNA (FST = 0.001, P = 0.291) and microsatellite data (FST = 0.003, P = 0.008). Pairwise F-statistic values generated from mtDNA and microsatellite DNA were similar, showing little evidence of significant genetic differentiation. The minimum spanning haplotype network constructed using mtDNA control regions produced no clear phylogeographic structure. The Mantel test revealed no significant correlation with distances for both mtDNA and microsatellite DNA. Therefore, our results suggest a panmictic population of Japanese eels in China, which should be conserved as a single management unit.


Assuntos
Enguias/genética , Espécies em Perigo de Extinção , Repetições de Microssatélites/genética , População/genética , Animais , China , DNA Mitocondrial/genética , Enguias/crescimento & desenvolvimento , Genética Populacional , Filogenia
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