人间充质干细胞脂肪形成和成骨细胞形成同时共享的候选基因的鉴定。

IF 1.7 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Folia histochemica et cytobiologica Pub Date : 2022-05-16 DOI:10.5603/FHC.a2022.0012
Xia Yi, Ping Wu, Yu-Fen Fan, Y. Gong, Jianyun Liu, Jianjun Xiong, Xiaoyun Xu
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引用次数: 3

摘要

引言在骨质疏松领域,临床上已经很好地确定了骨形成和脂质积累之间的关系。尽管许多分子已经被很好地记录了脂肪生成和成骨细胞生成(脂肪成骨细胞发生),但相互转录调控仍有待探索。材料和方法在此,我们试图通过RNA-Seq技术使用人间充质干细胞(hMSCs)鉴定脂肪细胞/成骨细胞在第3、5和7天分化的常见候选基因。通过RNA干扰(RNAi),我们通过油红/茜素红/碱性磷酸酶(ALPL)染色和qRT-PCR(实时定量PCR)进一步证实了候选基因在脂肪成骨细胞发生过程中的功能,尤其是下调基因最普遍和PI3K-AKT信号通路最富集的情况下,这两种分化事件同时共享。利用慢病毒系统,我们进一步证实ANKRD1(锚蛋白重复结构域1)通过RNA干扰(RNAi)促进脂肪生成和抑制成骨细胞生成,IGF1(胰岛素样生长因子1)基于生物标志物的基因表达和蛋白质积累以及细胞表型特性同时促进脂肪成骨细胞的生成。结论本研究将为控制脂肪细胞/成骨细胞平衡或hMSCs命运选择提供潜在的分子开关,并为筛选代谢性骨病骨质疏松症的研究和治疗靶点提供线索。
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Identification of candidate genes simultaneously shared by adipogenesis and osteoblastogenesis from human mesenchymal stem cells.
INTRODUCTION In osteoporosis field, it had been clinically well established a given relationship between bone formation and lipid accumulation. Although numerous molecules had been well documented for adipogenesis and osteoblastogenesis (adipo-osteoblastogenesis), the reciprocal transcriptional regulation still remained to be explored. MATERIAL AND METHODS Here, we tried to identify the common candidate genes of adipocyte/osteoblastocyte differentiation at 3, 5, and 7 days using human mesenchymal stem cells (hMSCs) via RNA-Seq technique. By using RNA interference (RNAi), we further confirmed the function of candidate genes during adipo-osteoblastogenesis through Oil Red/Alizarin Red/alkaline phosphatase (ALPL) staining and qRT-PCR (quantitative real-time PCR). RESULTS The identified 275 significantly differentially expressed genes (DEGs), especially with the down-regulated genes most prevalent and PI3K-AKT signaling pathway mostly enriched, were simultaneously shared by both differentiation events. Using lentiviral system, we further confirmed that ANKRD1 (ankyrin repeat domain 1) promoted adipogenesis and inhibited osteoblastogenesis via RNA interference (RNAi), and IGF1 (insulin like growth factor 1) simultaneously facilitated adipo-osteoblastogenesis on the base of gene expression and protein accumulation of biomarkers and cellular phenotype property. CONCLUSION This study would provide the potential molecular switches to control the adipocyte/osteoblastocyte balance or hMSCs fate choices and clues to screen the study and therapy targets of metabolic bone disease osteoporosis.
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来源期刊
Folia histochemica et cytobiologica
Folia histochemica et cytobiologica 生物-生化与分子生物学
CiteScore
2.80
自引率
6.70%
发文量
56
审稿时长
6-12 weeks
期刊介绍: "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.
期刊最新文献
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