Role of wnt-5a in the determination of human mesenchymal stem cells to preadipocytes

Bilkovski, R.; Oberhäuser, F.; Droste, Andrea; Krone, W.; Laudes, Matthias

doi:10.1055/s-2008-1076223

Cited by 9 publications

(12 citation statements)

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“…Wnt5a also functions in postnatal cellular differentiation and tissue homeostasis. In particular, Wnt5a has a role in hematopoiesis (Liang et al, 2003) and mesenchymal stem cell differentiation (Yang et al, 2003;Bilkovski et al, 2010). Mechanistically, Wnt5a-initiated cell signaling leads to altered cell function through rearrangements of the cytoskeleton and/or changes in gene expression (reviewed in Kikuchi et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Differential Regulation of the Mouse and HumanWnt5aAlternative Promoters A and B

Katula

Joyner-Powell

Hsu

et al. 2012

DNA and Cell Biology

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Wnt5a is an extracellular glycoprotein that activates Wnt signaling pathways, important in development and tissue homeostasis. Wnt5a expression is often misregulated during cancer progression. In this study, we analyzed the transcriptional regulation of two of the Wnt5a alternative promoters, termed A and B. Transient transfection of promoter A and B luciferase reporter constructs in to NIH3T3 and Caco-2 cells indicated that the separated promoters are both functional and that 300-450 base pair (bp) of upstream sequence is sufficient for activity. Promoter B constructs displayed distinct patterns of expression in the two cell types. The endogenous levels of promoter A-derived transcripts were found to be greater than the promoter B transcripts by four- to sixfold in fibroblast cells. Treatment of NIH3T3 cells with tumor necrosis factor (TNF)-alpha leads to an increase in both promoter A and B activities, but promoter B was more responsive. Using inhibitors of TNF-alpha effector proteins, we provide evidence that the transcription factor nuclear factor-kappaB and the MEK1/2 and p38 kinases have distinct roles in determining the activity levels of promoters, A and B. These results support the conclusion that Wnt5a promoters, A and B, are differentially regulated and provide a model for complex transcriptional regulation of Wnt5a.

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Section: Introductionmentioning

confidence: 99%

Differential Regulation of the Mouse and HumanWnt5aAlternative Promoters A and B

Katula

Joyner-Powell

Hsu

et al. 2012

DNA and Cell Biology

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“…The Wnt proteins are a family of secreted glycoproteins that signal through a cell surface receptor known as frizzled. WNT5A could act as an important proinflammatory factor by upregulating the serine-threonine kinase c-Jun N-terminal kinase 1 (9,10). It is believed that SFRP5 binding to WNT5A attenuates Wnt signaling (11,12), thereby restraining the chronic inflammatory state and improving insulin sensitivity (5).…”

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confidence: 99%

Balanced duo of anti-inflammatory SFRP5 and proinflammatory WNT5A in children

et al. 2014

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“…(A‐ii)]. As previously noted, C3H10T1/2 cells have superior transfection efficiencies and similar differentiation capacities to MSCs and were therefore used as an MSC‐surrogate for investigation of cell‐cell contact formation and subsequent signaling pathway analysis . In contrast to hydrogel encapsulated cells, C3H10T1/2 pellets [Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Mouse embryonic fibroblasts (C3H10T1/2, Clone 8) were obtained from American Type Culture Collection (ATCC; Manassas, VA) and maintained at 37°C with 5% CO 2 in Basal Eagle's Medium (Cellgro) with 10% FBS, 100 U/mL penicillin, 100 μg/mL streptomycin, and 0.25 μg/mL amphotericin B. C3H10T1/2 cells were used as a surrogate for MSCs due to their superior transfection efficiencies and similar differentiation capacities …”

Section: Methodsmentioning

confidence: 99%

Disruption of cell-cell contact-mediated notch signaling via hydrogel encapsulation reduces mesenchymal stem cell chondrogenic potential

Chen

Hoffman

Chen

et al. 2014

J. Biomed. Mater. Res.

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Cell-cell contact-mediated Notch signaling is essential for mesenchymal stem cell (MSC) chondrogenesis during development. However, subsequent deactivation of Notch signaling is also required to allow for stem cell chondrogenic progression. Recent literature has shown that Notch signaling can also influence Wnt/β-catenin signaling, critical for MSC differentiation, through perturbations in cell-cell contacts. Traditionally, abundant cell-cell contacts, consistent with development, are emulated in vitro using pellet cultures for chondrogenesis. However, cells are often encapsulated within biomaterials-based scaffolds, such as hydrogels, to improve therapeutic cell localization in vivo. To explore the role of Notch and Wnt/β-catenin signaling in the context of hydrogel-encapsulated MSC chondrogenesis, we compared signaling and differentiation capacity of MSCs in both hydrogels and traditional pellet cultures. We demonstrate that encapsulation within poly(ethylene glycol) (PEG) hydrogels reduces cell-cell contacts, and both Notch (7.5-fold) and Wnt/β-catenin (84.7-fold) pathway activation. Finally, we demonstrate that following establishment of cell-cell contacts and transient Notch signaling in pellet cultures, followed by Notch signaling deactivation, resulted in a 1.5-fold increase in MSC chondrogenesis. Taken together, these findings support that cellular condensation, and the establishment of initial cell-cell contacts is critical for MSC chondrogenesis, and this process is inhibited by hydrogel encapsulation.

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Role of wnt-5a in the determination of human mesenchymal stem cells to preadipocytes

Cited by 9 publications

References 0 publications

Differential Regulation of the Mouse and HumanWnt5aAlternative Promoters A and B

Differential Regulation of the Mouse and HumanWnt5aAlternative Promoters A and B

Balanced duo of anti-inflammatory SFRP5 and proinflammatory WNT5A in children

Disruption of cell-cell contact-mediated notch signaling via hydrogel encapsulation reduces mesenchymal stem cell chondrogenic potential

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