miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

Gu, C.; Xu, Yan; Zhang, Shanfeng; Guan, Hongya; Shi, Song; Wang, Xiuli; Wang, Yisheng; Li, Yuebai; Zhao, Guoqiang

doi:10.1038/srep38491

Cited by 97 publications

(90 citation statements)

References 42 publications

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“…Meanwhile, suppressed osteogenic activity has been detected in ONFH patients [15]. Restoration of osteogenic potential could alleviate the progression of ONFH in animal experiments [16]. Hence, we mainly focused on the rescue of ethanol-induced anti-osteogenic effects to reduce the development of alcohol-induced ONFH.…”

Section: Introductionmentioning

confidence: 99%

The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head

Chen¹,

Zhu²,

Xu³

et al. 2017

Cell Physiol Biochem

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Background: Alcohol abuse is known to be a leading risk factor for atraumatic osteonecrosis of the femoral head (ONFH), in which the suppression of osteogenesis plays a critical role. Cordycepin benefits bone metabolism; however, there has been no study to determine its effect on osteonecrosis. Methods: Human bone mesenchymal stem cells (hBMSCs) were identified by multi-lineage differentiation. Alkaline phosphatase (ALP) activity, RT-PCR, western blots, immunofluorescent assay and Alizarin red staining of BMSCs were evaluated. A rat model of alcohol-induced ONFH was established to investigate the protective role of cordycepin against ethanol. Hematoxylin & eosin (H&E) staining and micro-computerized tomography (micro-CT) were performed to observe ONFH. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining was carried out to detect OCN and COL1. Results: Ethanol significantly suppressed ALP activity, decreased gene expression of OCN and BMP2, lowered levels of RUNX2 protein, and reduced immunofluorescence staining of OCN and COL1 and calcium formation of hBMSCs. However, these inhibitory effects were attenuated by cordycepin co-treatment at concentrations of 1 and 10 µg/mL Moreover, it was revealed that the osteo-protective effect of cordycepin was associated with modulation of the Wnt/β-catenin pathway. In vivo, by micro-CT, TUNEL and immunohistochemical staining of OCN and COL1, we found that cordycepin administration prevented alcohol-induced ONFH. Conclusion: Cordycepin treatment to enhance osteogenesis may be considered a potential therapeutic approach to prevent the development of alcohol-induced ONFH.

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Section: Introductionmentioning

confidence: 99%

The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head

Chen¹,

Zhu²,

Xu³

et al. 2017

Cell Physiol Biochem

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“…[24][25][26][27] Several recent studies also suggested that miRNAs might take part in the development of ONFH. [28][29][30] To date, alterations in circulating miRNAs in steroid-associated ONFH remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNA signature of steroid‐induced osteonecrosis of the femoral head

Zheng

Jiang

et al. 2017

Cell Proliferation

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ObjectivesSteroid‐induced osteonecrosis of the femoral head (ONFH) is a common orthopaedic disease of which early detection remains clinically challenging. Accumulating evidences indicated that circulating microRNAs (miRNAs) plays vital roles in the development of several bone diseases. However, the association between circulating miRNAs and steroid‐induced ONFH remains elusive.Materials and methodsmiRNA microarray was performed to identify the differentially abundant miRNAs in the serums of systemic lupus erythematosus (SLE) patients with steroid‐induced ONFH as compared with SLE control and healthy control group. We predicted the potential functions of these differentially abundant miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and reconstructed the regulatory networks of miRNA‐mRNA interactions.ResultsOur data indicated that there were 11 differentially abundant miRNAs (2 upregulated and 9 downregulated) between SLE‐ONFH group and healthy control group and 42 differentially abundant miRNAs (14 upregulated and 28 downregulated) between SLE‐ONFH group and SLE control group. We also predicted the potential functions of these differentially abundant miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses and reconstructed the regulatory networks of miRNA‐mRNA interactions.ConclusionsThese findings corroborated the idea that circulating miRNAs play significant roles in the development of ONFH and may serve as diagnostic markers and therapeutic targets.

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“…miRNAs are 18-24 nucleotides, single-stranded, non-coding RNA. They have been proven to be involved in various tissues and biological functions [29]. For example, miR-141 and miR-200a have been reported to regulate osteoblast differentiation by targeting the BMP-2 signaling pathway [30].…”

Section: Discussionmentioning

confidence: 99%

MiR-27b Impairs Adipocyte Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting LPL

Hu¹,

Tang²,

Hu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: In this study, the molecular mechanisms of miR-27b and lipoprotein lipase (LPL) that regulate human adipose-derived mesenchymal stem cells (hASCs) adipogenic differentiation were detected. Methods: Microarray analysis was applied to screen for differentially expressed miRNAs and mRNA during hASCs adipocyte differentiation induction. MiR-27b and LPL were found to have abnormal expression. Then, a dual luciferase reporter assay was employed to validate the targeting relationship between miR-27b and LPL. We also utilized qRT-PCR, western blot, cellular immunofluorescence and an oil red O staining assay to analyze the regulation of miR-27b and LPL during adipogenic differentiation. Results: The microarray analysis demonstrated that, during adipogenic differentiation, miR-27b was down-regulated, while LPL was up-regulated but tended to become stable 14 days after induction. A dual luciferase reporter assay confirmed the negative targeting regulatory relationship between miR-27b and LPL. After overexpressing and silencing miR-27b, LPL was found to be reversely regulated by miR-27b according to qRT-PCR and western blot. The fat-formation-related biomarkers CCAAT-enhancer binding protein α (c/EBPα) and peroxisome proliferator-activated receptors γ (PPARγ) had decreasing levels after over-expressing miR-27b or knockdown of LPL followed by adipogenic differentiation. Meanwhile, the oil red O staining assay revealed that the accumulation of lipid droplets decreased. There was no change in the expression of c/EBPα, PPARγ, or lipid droplet accumulation when overexpressing miR-27b and LPL. Conclusion: During the adipogenic differentiation of hASCs, miR-27b expression decreased, and LPL expression increased. The abnormal expression of miR-27b and LPL effectively regulated the adipogenic differentiation of hASCs.

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miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1

Cited by 97 publications

References 42 publications

The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head

The Protective Effect of Cordycepin On Alcohol-Induced Osteonecrosis of the Femoral Head

Circulating microRNA signature of steroid‐induced osteonecrosis of the femoral head

MiR-27b Impairs Adipocyte Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells by Targeting LPL

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