Fibroblast growth factors 1 and 2 inhibit adipogenesis of human bone marrow stromal cells in 3D collagen gels

Blanc, Solange Le; Simann, Meike; Jakob, Franz; Schütze, Norbert; Schilling, Tatjana

doi:10.1016/j.yexcr.2015.09.009

Cited by 17 publications

(25 citation statements)

References 58 publications

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“…Fig. S1 and S2), which were in line with earlier results on hBMSCs differentiated in 3D hydrogels [Le Blanc et al, ]. Lipidogenesis (Suppl.…”

Section: Resultssupporting

confidence: 91%

“…These results suggest that the seemingly pro‐osteogenic effect of FGF1 and 2 was a reversal of either commitment and that hBMSCs were entrapped in a pre‐commitment state, independently of an already pursued differentiation pathway. In line, the prevention of adipogenesis by FGF1 and 2, which was reported earlier in 3D hydrogels [Le Blanc et al, ], was verified in our 2D system. Our results suggest that the strong downregulation of the adipogenic key transcription factor PPARγ2, which is known to activate further adipogenic marker genes and to drive adipogenic differentiation, is responsible for the inhibitory effect [Lowe et al, ].…”

Section: Discussionsupporting

confidence: 92%

“…In this study, we revealed that FGF1 and 2 diminished the osteogenic differentiation of primary bone marrow cells of human origin. Furthermore, osteogenic markers were not promoted by FGF addition in adipogenic conditions and the anti‐adipogenic effect described earlier in 3D cultures [Le Blanc et al, ] was confirmed in our system. The results displayed a high reproducibility over the different donors stating their reliability.…”

Section: Discussionsupporting

confidence: 86%

“…By deploying microarray analysis, our group identified FGF1 and 2 as potential key factors associated with lineage decisions of skeletal precursors [Schilling et al, ]. Further research on the effects of canonical FGF signaling on adipogenic differentiation using 3D collagen hydrogels confirmed an inhibitory effect on adipogenesis [Le Blanc et al, ]. Hence we wanted to clarify and extend the knowledge about the effects of FGF1/2 on lineage decisions in primary human BMSCs.…”

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confidence: 99%

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Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

et al. 2016

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Controlling the adipo-osteogenic lineage decision of trabecular human bone marrow stromal cells (hBMSCs) in favor of osteogenesis represents a promising approach for osteoporosis therapy and prevention. Previously, Fibroblast Growth Factor 1 (FGF1) and its subfamily member FGF2 were scored as leading candidates to exercise control over skeletal precursor commitment and lineage decision albeit literature results are highly inconsistent. We show here that FGF1 and 2 strongly prevent the osteogenic commitment and differentiation of hBMSCs. Mineralization of extracellular matrix (ECM) and mRNA expression of osteogenic marker genes Alkaline Phosphatase (ALP), Collagen 1A1 (COL1A1), and Integrin-Binding Sialoprotein (IBSP) were significantly reduced. Furthermore, master regulators of osteogenic commitment like Runt-Related Transcription Factor 2 (RUNX2) and Bone Morphogenetic Protein 4 (BMP4) were downregulated. When administered under adipogenic culture conditions, canonical FGFs did not support osteogenic marker expression. Moreover despite the presence of osteogenic differentiation factors, FGFs even disabled the pro-osteogenic lineage decision of pre-differentiated adipocytic cells. In contrast to FGF Receptor 2 (FGFR2), FGFR1 was stably expressed throughout osteogenic and adipogenic differentiation and FGF addition. Moreover, FGFR1 and Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2) were found to be responsible for underlying signal transduction using respective inhibitors. Taken together, we present new findings indicating that canonical FGFR-ERK1/2 signaling entrapped hBMSCs in a pre-committed state and arrested further maturation of committed precursors. Our results might aid in unraveling and controlling check points relevant for ageing-associated aberrant adipogenesis with consequences for the treatment of degenerative diseases such as osteoporosis and for skeletal tissue engineering strategies. J. Cell. Biochem. 118: 263-275, 2017. © 2016 Wiley Periodicals, Inc.

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“…Fig. S1 and S2), which were in line with earlier results on hBMSCs differentiated in 3D hydrogels [Le Blanc et al, ]. Lipidogenesis (Suppl.…”

Section: Resultssupporting

confidence: 91%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 86%

mentioning

confidence: 99%

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Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

et al. 2016

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“…FGFs are also crucial for the regulation of MSCs chondrogenic differentiation through FGF/FGFR3, as demonstrated by their involvement in the pathogenesis of different forms of chondrodysplasia (Ornitz and Legeai-Mallet, 2017). However, also for these GFs, results in literature are discordant: recent data indicate that FGF1 and FGF2 maintain MSCs in an uncommitted state, preventing their differentiation (Le Blanc et al, 2015; Simann et al, 2017). Finally, the hormone-like FGF23, produced by bone cells and by cells of different tissues, favors osteogenic differentiation at the expenses of adipogenesis by binding to its receptor Klotho, which mediates the activation of MAPKs signaling (Li et al, 2013c).…”

Section: Microenvironment Factors Orchestrate Mscs Fatementioning

confidence: 99%

Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

Sobacchi

Palagano

Villa

et al. 2017

Front. Bioeng. Biotechnol.

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Mesenchymal stem cells (MSCs) are multipotent stromal cells that are identified by in vitro plastic adherence, colony-forming capacity, expression of a panel of surface molecules, and ability to differentiate at least toward osteogenic, adipogenic, and chondrogenic lineages. They also produce trophic factors with immunomodulatory, proangiogenic, and antiapoptotic functions influencing the behavior of neighboring cells. On the other hand, a reciprocal regulation takes place; in fact, MSCs can be isolated from several tissues, and depending on the original microenvironment and the range of stimuli received from there, they can display differences in their essential characteristics. Here, we focus mainly on the bone tissue and how soluble factors, such as growth factors, cytokines, and hormones, present in this microenvironment can orchestrate bone marrow-derived MSCs fate. We also briefly describe the alteration of MSCs behavior in pathological settings such as hematological cancer, bone metastasis, and bone marrow failure syndromes. Overall, the possibility to modulate MSCs plasticity makes them an attractive tool for diverse applications of tissue regeneration in cell therapy. Therefore, the comprehensive understanding of the microenvironment characteristics and components better suited to obtain a specific MSCs response can be extremely useful for clinical use.

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Key‐genes regulating the liposecretion process of mature adipocytes

Maurizi

Petäistö

Maurizi³

et al. 2017

Journal Cellular Physiology

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White mature adipocytes (MAs) are plastic cells able to reversibly transdifferentiate toward fibroblast-like cells maintaining stem cell gene signatures. The main morphologic aspect of this transdifferentiation process, called liposecretion, is the secretion of large lipid droplets and the development of organelles necessary for exocrine secretion. There is a considerable interest in the adipocyte plastic properties involving liposecretion process, but the molecular details are incompletely explored. This review analyzes the gene expression of MAs isolated from human subcutaneous fat tissue with respect to bone marrow (BM)-derived mesenchymal stem cells (MSC) focusing on gene regulatory pathways involved into cellular morphology changes, cellular proliferation and transports of molecules through the membrane, suggesting potential ways to guide liposecretion. In particular, Wnt, MAPK/ERK, and AKT pathways were accurately described, studying up- and down-stream molecules involved. Moreover, adipogenic extra- and intra-cellular interactions were analyzed studying the role of CDH2, CDH11, ITGA5, E-Syt1, PAI-1, IGF1, and INHBB genes. Additionally, PLIN1 and PLIN2 could be key-genes of liposecretion process regulating molecules transport through the membrane. All together data demonstrated that liposecretion is regulated through a complex molecular networks that are able to respond to microenvironment signals, cytokines, and growth factors. Autocrine as well as external signaling molecules might activate liposecretion affecting adipocytes physiology.

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Fibroblast growth factors 1 and 2 inhibit adipogenesis of human bone marrow stromal cells in 3D collagen gels

Cited by 17 publications

References 58 publications

Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

Canonical FGFs Prevent Osteogenic Lineage Commitment and Differentiation of Human Bone Marrow Stromal Cells Via ERK1/2 Signaling

Soluble Factors on Stage to Direct Mesenchymal Stem Cells Fate

Key‐genes regulating the liposecretion process of mature adipocytes

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