microRNA‐148a‐3p in extracellular vesicles derived from bone marrow mesenchymal stem cells suppresses SMURF1 to prevent osteonecrosis of femoral head

Huang, Scott C.-H.; Li, Yaochun; Wu, Panfeng; Xiao, Yongbing; Duan, Ningbo; Quan, Jing; Du, Wei

doi:10.1111/jcmm.15766

Cited by 28 publications

(18 citation statements)

References 42 publications

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“…promoted the expression of cell cycle-related genes, including CDK2, CDK3, CDK4, CCNB, CCNG1, and CCND1, and signi cantly accelerated the cell cycle progression by decreasing the proportion of cells in G0/G1 phase by ow cytometry. The proliferation of bone marrow mesenchymal stem cell and non-smallcell lung cancer can also be promoted by miR-148a-3p mimic [41,42] which consistent with our present research. However, Bao et al and Wang et al have reported that overexpression of miR-148a-3p inhibited the proliferation of gastric cancer cells [43] and diabetic retinopathy cell model [44], respectively.…”

Section: Discussionsupporting

confidence: 89%

MicroRNA Profiling Reveals an Abundant ssc-miRNA-148a-3p that Promotes Proliferation and Differentiation during Intramuscular Adipogenesis in Chinese Guizhou Congjiang Pigs Breeds by targeting PPARGC1A

Tan

Chen

Teng

et al. 2021

Preprint

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BackgroundIntramuscular fat development is regulated by a series of complicated processes, and non-coding RNA (ncRNA) such as microRNA (miRNA) plays a critical role during intramuscular preadipocyte proliferation and differentiation development in pigs. In present research, we detected the expression profiles of miRNA during different differentiation stages, namely, day 0 (D0), day 4 (D4), and day 8 (D8), of intramuscular preadipocytes from the longissimus dorsi muscle of Chinese Guizhou Congjiang pigs to provide first insights into their potential involvement in intramuscular preadipocyte development. And we investigated the function of miR-148a-3p in adipocyte proliferation, apoptosis, and differentiation. ResultsA total of 67, 95, and 16 differentially expressed (DE) miRNAs were detected between D4 and D0, between D8 and D0, and between D8 and D4, respectively. We further characterized the role of miR-148a-3p which was differentially expressed and highest expressed abundance in D0, D4, and D8. To explore the role of miR-148a-3p in porcine intramuscular preadipocyte, miR-148a-3p mimics and inhibitors were used to perform miR-148a-3p overexpression and knockdown, respectively. Overexpression of miRNA-148a-3p increased the number of intramuscular preadipocytes in the S/G2 phase of the cell cycle and decreased the proportion of cells in the G0/G1 phase. Moreover, it promoted proliferation by regulation of cyclin B, cyclin G1, cyclin D1, CDK2, CDK3, and CDK4 and inhibited apoptosis of intramuscular preadipocyte by regulating the expression of Caspase-3, Bax, and Bcl-2. Meanwhile, the mimics of miR-148a-3p dramatically promoted intramuscular preadipocyte differentiation and upregulated the expression levels of adipogenic marker genes PPARγ, FASN, FABP4, HSL, APOE, LPL, and CEBPα. Furthermore, miR-148a-3p promoted intramuscular preadipocyte differentiation via restraining the AMPK/ACC/CPT1C signaling pathway. PPARGC1A was identified as a target gene of miR-148a-3p by luciferase activity and western blotting assays. ConclusionOur study provides novel insights into the regulatory mechanisms underlying intramuscular preadipocyte development and identified amount of miRNAs whose regulatory potential will need to be explored in the future. Our results establish that miR-148a-3p promoted adipocyte differentiation by targeting PPARGC1A.

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Section: Discussionsupporting

confidence: 89%

MicroRNA Profiling Reveals an Abundant ssc-miRNA-148a-3p that Promotes Proliferation and Differentiation during Intramuscular Adipogenesis in Chinese Guizhou Congjiang Pigs Breeds by targeting PPARGC1A

Tan

Chen

Teng

et al. 2021

Preprint

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“…For example, miR-155-5p was found to be significantly downregulated in ONFH samples [ 16 ]. miR-148a-3p [ 17 ], miR-23b-3p [ 18 ], and miR-26a [ 19 ] were all reported to play a protective role against ONFH. Recent advancement of genome-wide profiling approaches, such as gene microarray and RNA-sequencing technology, enhances the understanding of miRNA and gene expression profiles in the context of ONFH, providing opportunity to identify novel biomarkers and therapeutic targets for ONFH [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

Yu¹,

Yao

Jiang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Osteonecrosis of the femoral head (ONFH) accounts for as many as 18% of total hip arthroplasties. Knowledge of genetic changes and molecular abnormalities could help identify individuals considered to be at a higher risk of developing ONFH. In this study, we sought to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) associated with ONFH by integrated bioinformatics analyses as well as to construct the miRNA-mRNA regulatory network involving in the pathogenesis of ONFH. We performed differential expression analysis using a gene expression profile GSE123568 and a miRNA expression profile GSE89587 deposited in the Gene Expression Omnibus and identified 47 DEmiRs (24 upregulated miRNAs and 23 downregulated miRNAs) and 529 DEGs (218 upregulated genes and 311 downregulated genes). Gene Ontology enrichment analyses of DEGs suggested that DEGs were significantly enriched in neutrophil activation, cytosol, and ubiquitin-protein transferase activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs revealed that DEGs were significantly enriched in transcriptional misregulation in cancer. DEGs-based miRNA-mRNA regulatory networks were obtained by searching miRNA-mRNA prediction databases, TargetScan, miTarBase, miRMap, miRDB, and miRanda databases. Then, overlapped miRNAs were selected between these putative miRNAs and DEmiRs between ONFH and non-ONFH, and pairs of the DEmiR-DEG regulatory network were finally depicted. There were 12 nodes and 64 interactions for upDEmiR-downDEG regulatory networks and 6 nodes and 16 interactions for downDEmiR-upDEG regulatory networks. Using the STRING database, we established a protein-protein interaction network based on the overlapped DEGs between ONFH and non-ONFH. C5AR1, CDC27, CDC34, KAT2B, CPPED1, TFDP1, and MX2 were identified as the hub genes. The present study characterizes the miRNA profile, gene profile, and miRNA-mRNA regulatory network in ONFH, which may contribute to the interpretation of the pathogenesis of ONFH and the identification of novel biomarkers and therapeutic targets for ONFH.

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“…This is a fascinating question suggesting that understanding the composition of “hypoxic” vs. “normoxic” EVs could provide valuable information on the key regulators of pathologic states. Indeed, identification of microRNA-148a-3p as the mediator of the beneficial effect of BMSC EVs on osteonecrosis confirmed the role of SMURF1 in the pathogenesis [ 132 ]. Similarly, identification of targets of the BMSC EV cargo miRNA-375, that mediate anti-cancer effect on cervical cancer, might reveal further components in the transformation of cervical epithelium [ 92 ].…”

Section: Discussionmentioning

confidence: 96%

Extracellular Vehicles of Oxygen-Depleted Mesenchymal Stromal Cells: Route to Off-Shelf Cellular Therapeutics?

Gala

Mohak

Fábián

2021

Cells

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Cellular therapy is a promising tool of human medicine to successfully treat complex and challenging pathologies such as cardiovascular diseases or chronic inflammatory conditions. Bone marrow-derived mesenchymal stromal cells (BMSCs) are in the limelight of these efforts, initially, trying to exploit their natural properties by direct transplantation. Extensive research on the therapeutic use of BMSCs shed light on a number of key aspects of BMSC physiology including the importance of oxygen in the control of BMSC phenotype. These efforts also led to a growing number of evidence indicating that the beneficial therapeutic effects of BMSCs can be mediated by BMSC-secreted agents. Further investigations revealed that BMSC-excreted extracellular vesicles could mediate the potentially therapeutic effects of BMSCs. Here, we review our current understanding of the relationship between low oxygen conditions and the effects of BMSC-secreted extracellular vesicles focusing on the possible medical relevance of this interplay.

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microRNA‐148a‐3p in extracellular vesicles derived from bone marrow mesenchymal stem cells suppresses SMURF1 to prevent osteonecrosis of femoral head

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 28 publications

References 42 publications

MicroRNA Profiling Reveals an Abundant ssc-miRNA-148a-3p that Promotes Proliferation and Differentiation during Intramuscular Adipogenesis in Chinese Guizhou Congjiang Pigs Breeds by targeting PPARGC1A

MicroRNA Profiling Reveals an Abundant ssc-miRNA-148a-3p that Promotes Proliferation and Differentiation during Intramuscular Adipogenesis in Chinese Guizhou Congjiang Pigs Breeds by targeting PPARGC1A

Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head

Extracellular Vehicles of Oxygen-Depleted Mesenchymal Stromal Cells: Route to Off-Shelf Cellular Therapeutics?

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