SERPINB2 is a novel TGFβ-responsive lineage fate determinant of human bone marrow stromal cells

Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad; Dawud, Raed Abu; Almalki, Sami G.; Kaimkhani, Zahid Ali; Aldahmash, Abdullah; Alajez, Nehad M.; Alfayez, Musaad; Kassem, Moustapha; Mahmood, Amer

doi:10.1038/s41598-017-10983-x

Cited by 20 publications

(20 citation statements)

References 38 publications

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“…Recent studies have showed that TGF-β promoted adipocyte commitment. The difference was that they studied the adipocyte commitment of BMSCs isolated from different species: mice and humans [45,47]. MSC origin may affect adipocyte commitment under TGF-β signaling.…”

Section: Resultsmentioning

confidence: 99%

“…Although some studies have reported that TGF-β suppresses the adipocyte commitment of MSCs, recent studies showed that TGF-β promotes adipocyte commitment. A single pulse dose treatment with TGF-β during the commitment phase led to increased adipogenesis of human BMSCs, while continuous treatment during the whole phase (commitment phase and differentiation phase) inhibited adipogenesis [47]. The reason could be TGF-β promoted the first step adipocyte commitment, but inhibited the second step adipogenic differentiation of BMSCs by repressing the function of C/EBPβ and C/EBPδ during the differentiation phase [68].…”

Section: Tgf-β Signaling In the Adipocyte Commitment Of Mscsmentioning

confidence: 99%

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TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment

2020

Stem Cell Res Ther

125

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Adipocytes arising from mesenchymal stem cells (MSCs) requires MSC adipocyte commitment and differentiation of preadipocytes to mature adipocytes. Several signaling and some cytokines affect the adipogenesis of MSCs. This review focuses on the roles of TGF-β/SMAD signaling in adipocyte commitment of MSCs. BMP4 and BMP7 signaling are sufficient to induce adipocyte lineage determination of MSCs. The roles of BMP2, TGF-β, and myostatin signaling in this process are unclear. Other TGF-β/SMAD signaling such as BMP3 and BMP6 signaling have almost no effect on commitment because of limited research available, while GDF11 signaling inhibits adipocyte commitment in human MSCs. In this review, we summarize the available information on TGF-β/SMAD signaling regulation of MSCs in adipocyte commitment. Deeper study of this commitment mechanism will offer new approaches in treating obesity, diabetes mellitus, and obesity-related metabolism syndrome.

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Section: Resultsmentioning

confidence: 99%

Section: Tgf-β Signaling In the Adipocyte Commitment Of Mscsmentioning

confidence: 99%

TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment

2020

Stem Cell Res Ther

125

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“…Transforming growth factor beta 1 is the most abundant growth factor in bone matrix and regulates cell growth and differentiation. Human bone marrow mesenchymal stromal/stem cells (BM-MSCs) treated with TGF-β1 for up to 7 days, showed reduced adipogenic differentiation in favour of osteogenic differentiation [55]. Global gene expression analysis revealed that serpin peptidase inhibitor clade B (ovalbumin) member 2 (SERPINB2) was significantly downregulated in TGF-β1 treated cells.…”

Section: Tgf-β Signallingmentioning

confidence: 99%

Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

Ambele

Dhanraj

Giles

2020

IJMS

199

146

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The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte commitment. Conversely, over a dozen molecular players including transcription factors, genes, signalling pathways, epigenetic regulators, and microRNAs have been described to be involved in the differentiation of preadipocytes to adipocytes; however, only peroxisome proliferator-activated receptor gamma has proven to be clinically relevant. A detailed understanding of how the molecular players underpinning adipogenesis relate to adipose tissue function could provide new therapeutic approaches for addressing obesity without compromising adipose tissue function.

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“…Not completely immortalized because E6/E7 was sufficient to extend lifespan but not to bypass senescence 4. Probably incompletely immortalized 5 [30,68,69]. employed hMSC-hTERT-derived clones.…”

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confidence: 99%

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research

Piñeiro-Ramil

Sanjurjo‐Rodríguez

Castro-Viñuelas

et al. 2019

IJMS

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The unavailability of sufficient numbers of human primary cells is a major roadblock for in vitro repair of bone and/or cartilage, and for performing disease modelling experiments. Immortalized mesenchymal stromal cells (iMSCs) may be employed as a research tool for avoiding these problems. The purpose of this review was to revise the available literature on the characteristics of the iMSC lines, paying special attention to the maintenance of the phenotype of the primary cells from which they were derived, and whether they are effectively useful for in vitro disease modeling and cell therapy purposes. This review was performed by searching on Web of Science, Scopus, and PubMed databases from 1 January 2015 to 30 September 2019. The keywords used were ALL = (mesenchymal AND ("cell line" OR immortal*) AND (cartilage OR chondrogenesis OR bone OR osteogenesis) AND human). Only original research studies in which a human iMSC line was employed for osteogenesis or chondrogenesis experiments were included. After describing the success of the immortalization protocol, we focused on the iMSCs maintenance of the parental phenotype and multipotency. According to the literature revised, it seems that the maintenance of these characteristics is not guaranteed by immortalization, and that careful selection and validation of clones with particular characteristics is necessary for taking advantage of the full potential of iMSC to be employed in bone and cartilage-related research.

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SERPINB2 is a novel TGFβ-responsive lineage fate determinant of human bone marrow stromal cells

Cited by 20 publications

References 38 publications

TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment

TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment

Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

Usefulness of Mesenchymal Cell Lines for Bone and Cartilage Regeneration Research

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