Gas7 mediates the differentiation of human bone marrow‐derived mesenchymal stem cells into functional osteoblasts by enhancing Runx2‐dependent gene expression

Hung, Feng‐Chun; Chang, Yu‐Han; Lin‐Chao, Sue; Chao, Chuck C.‐K.

doi:10.1002/jor.21425

Cited by 10 publications

(13 citation statements)

References 28 publications

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“…Among these targets are the receptor for Wnt proteins frizzled-class-receptor-3 (FZD3), involved in MSCs differentiation into hepatocytes 55 and the zinc-finger-protein-91 (ZFP91), which affect engraftment of hematopoietic stem cells 56 . Similarly, growth-arrest specific gene-7 (Gas7) and S/G2 cyclin, cyclin G2 (CCNG2), targets of mir378, regulate stem cell differentiation 57, 58 . Other targets of miR378 include genes related mainly to mitochondria, transcription, cytoskeleton, calcium signaling, apoptosis, and proteolysis, underscoring the versatility of EV-miRNA.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells

Eirin

Riester

Zhu

et al. 2014

Gene

240

239

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Mesenchymal stromal/stem cells (MSCs) are clinically useful for cell-based therapy, but concerns regarding their ability to replicate limit their human application. MSCs release extracellular vesicles (EVs) that mediate at least in part the paracrine effects of the parental cells. To understand the molecular basis of their biological properties, we characterized the RNA cargo of EVs from porcine adipose-tissue derived MSCs. Comprehensive characterization of mRNA and miRNA gene expression using high-throughput RNA sequencing (RNA-seq) revealed that EVs are selectively enriched for distinct classes of RNAs. For example, EVs preferentially express mRNA for transcription factors (e.g. MDFIC, POU3F1, NRIP1) and genes involved in angiogenesis (e.g. HGF, HES1, TCF4) and adipogenesis (e.g. CEBPA, KLF7). EVs also express Golgi apparatus genes (ARRB1, GOLGA4) and genes involved in TGF-β signaling. In contrast, mitochondrial, calcium signaling, and cytoskeleton genes are selectively excluded from EVs, possibly because these genes remain sequestered in organelles or intracellular compartments. RNA-seq generated reads for at least 386 annotated miRNAs, but only miR148a, miR532-5p, miR378, and let-7f were enriched in EVs compared to MSCs. Gene ontology analysis indicates that these miRNA target transcription factors and genes that participate in several cellular pathways, including angiogenesis, cellular transport, apoptosis, and proteolysis. Our data suggest that EVs transport gene regulatory information to modulate angiogenesis, adipogenesis, and other cell pathways in recipient cells. These observations may contribute to development of regenerative strategies using EVs to overcome potential complications of cell-based therapy.

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Section: Discussionmentioning

confidence: 99%

MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells

Eirin

Riester

Zhu

et al. 2014

Gene

240

239

View full text Add to dashboard Cite

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“…Earlier, we also found a functional link between the expression of Gas7 and the processes of chondrogenesis and osteogenesis in human bone marrow-derived human MSCs [12, 13]. …”

Section: Gas7: a Pombe Cdc15 Homology Proteinmentioning

confidence: 86%

“…Recently, we observed that Gas7 represents a novel regulator of MSC-based osteogenesis [13]. Gas7 controls the differentiation of human MSCs into functional osteoblasts by enhancing Runx2-dependent gene expression.…”

Section: Gas7 In Msc-based Osteogenesismentioning

confidence: 99%

Gas7 Is Required for Mesenchymal Stem Cell-Derived Bone Development

Chao

Hung

Chao

2013

Stem Cells International

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Mesenchymal stem cells (MSCs) can differentiate into osteoblasts and lead to bone formation in the body. Osteoblast differentiation and bone development are regulated by a network of molecular signals and transcription factors induced by several proteins, including BMP2, osterix, and Runx2. We recently observed that the growth-arrest-specific 7 gene (Gas7) is upregulated during differentiation of human MSCs into osteoblasts. Downregulation of Gas7 using short-hairpin RNA decreased the expression of Runx2, a master regulator of osteogenesis, and its target genes (alkaline phosphatase, type I collagen, osteocalcin, and osteopontin). In addition, knockdown of Gas7 decreased the mineralization of dexamethasone-treated MSCs in culture. Conversely, ectopic expression of Gas7 induced Runx2-dependent transcriptional activity and gene expression leading to osteoblast differentiation and matrix mineralization. Genetic mutations of the Gas7 gene increased body fat levels and decreased bone density in mice. These results showed that Gas7 plays a role in regulating the pathways which are essential for osteoblast differentiation and bone development. In this review, we summarize the involvement of Gas7 in MSC-based osteogenesis and osteoporosis and describe the possible mechanisms responsible for the maintenance of cellular homeostasis in MSCs and osteoblasts.

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“…In particular, Gas7 induces neurite outgrowth. Report by Hung et al (2011) shows that Gas7 regulates mesenchymal stem cell differentiation. This implies that Gas7 has a role in cell differentiation process.…”

Section: )mentioning

confidence: 99%

Immunolocalization of Gas7 in the Subgranular Zone of Mice Hippocampus

Kumar

2019

Prague Med. Rep.

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It is established that neural stem cells (NSC) reside in the hippocampal subgranular zone (SGZ) and contribute to neurogenesis throughout life. Although the molecular events that regulate hippocampal neural stem cell differentiation are known, the precise mechanism is undefined. Here, the role of growth arrest specific 7 (Gas7) protein in SGZ neural progenitor cell differentiation was studied. Immunoblotting and immunohistochemistry for Gas7 were performed on 12 weeks old mice hippocampus. The results displayed a strong signal for Gas7 protein in the mice hippocampal tissue and SGZ cells, therefore suggesting that Gas7 might have a role in neural progenitor cell differentiation in SGZ.

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Gas7 mediates the differentiation of human bone marrow‐derived mesenchymal stem cells into functional osteoblasts by enhancing Runx2‐dependent gene expression

Cited by 10 publications

References 28 publications

MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells

MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells

Gas7 Is Required for Mesenchymal Stem Cell-Derived Bone Development

Immunolocalization of Gas7 in the Subgranular Zone of Mice Hippocampus

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