NO–β-catenin crosstalk modulates primitive streak formation prior to embryonic stem cell osteogenic differentiation

Ding, Huawen; Keller, Kevin C.; Martinez, Ivann Kenneth Carvajal; Geransar, Rose; Nieden, Kai O. zur; Nishikawa, Sandra; Rancourt, Derrick E.; Nieden, Nicole I. zur

doi:10.1242/dev.094151

Cited by 8 publications

(23 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemical modulators of NO included 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), a stable radical scavenger for NO [100 mM], and the exogenous NO donor S-nitroso-N-acetylpenicillamine (SNAP) [100 mM]. The flavoprotein binder diphenyleneiodonium (DPI) was used as a specific iNOS inhibitor [50 nM] and L-N 5 -(1-Iminoethyl)ornithine, dihydrochloride (L-NIO) as a specific inhibitor of eNOS [1 mM] as we have done before (Ding et al, 2012). All substances were dissolved in DMSO.…”

Section: Nos Inhibition/no Supplementationmentioning

confidence: 99%

“…In order to visualize the newly deposited calcified matrix, tetracycline (Molekula), which incorporates into newly synthesized matrix (Milch et al, 1958), was added to the culture medium at a final concentration of 35 mg/ml as described earlier (Ding et al, 2012;Trettner et al, 2014). The incorporated and autofluorescing tetracycline (Hallet et al, 1972) was visualized using the UV filter of a fluorescent microscope.…”

Section: Tetracycline Incorporationmentioning

confidence: 99%

“…A previous study in our laboratory using the iNOS and eNOS inhibitors diphenyleneiodonium (DPI) and L-N 5 -(1-Iminoethyl) ornithine (L-NIO) demonstrated that alkaline phosphatase metabolism is affected by eNOS, regulating the pre-osteoblast state during early osteogenic differentiation of ESCs (Ding et al, 2012). In this current study, we conducted time and differentiation-stage specific inhibition of iNOS and eNOS in the later phase of ESC osteogenesis coupled with analysis of calcium content (Fig.…”

Section: Isoform Specific Nos Inhibition In Split-phase Culturementioning

confidence: 99%

“…Based on our desire to further characterize the involvement of signaling pathways during ESC osteogenic differentiation, we have determined that increased levels of NO are generated during early ESC commitment (Ding et al, 2012). Concomitant with NO upregulation, expression of T-brachyury was enhanced, a gene which is predominantly expressed in the primitive streak in vivo.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Exogenous nitric oxide enhances calcification in embryonic stem cell-derived osteogenic cultures

et al. 2015

View full text Add to dashboard Cite

Section: Nos Inhibition/no Supplementationmentioning

confidence: 99%

Section: Tetracycline Incorporationmentioning

confidence: 99%

Section: Isoform Specific Nos Inhibition In Split-phase Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exogenous nitric oxide enhances calcification in embryonic stem cell-derived osteogenic cultures

et al. 2015

View full text Add to dashboard Cite

“…For example, a number of studies have shown that ESC aggregates treated with specific signaling molecules exhibit some of the molecular cascades and cell behaviors observed during normal gastrulation [93][94][95][96][97]. While these studies do not equate stem cells with embryos, several authors conclude that stem cell aggregates are surprisingly ''embryo like.''…”

Section: Behaving Like Part Of An Embryo or Merely Looking Like An Emmentioning

confidence: 99%

Totipotency: What It Is and What It Is Not

Condic

2014

Stem Cells and Development

111

View full text Add to dashboard Cite

There is surprising confusion surrounding the concept of biological totipotency, both within the scientific community and in society at large. Increasingly, ethical objections to scientific research have both practical and political implications. Ethical controversy surrounding an area of research can have a chilling effect on investors and industry, which in turn slows the development of novel medical therapies. In this context, clarifying precisely what is meant by ''totipotency'' and how it is experimentally determined will both avoid unnecessary controversy and potentially reduce inappropriate barriers to research. Here, the concept of totipotency is discussed, and the confusions surrounding this term in the scientific and nonscientific literature are considered. A new term, ''plenipotent,'' is proposed to resolve this confusion. The requirement for specific, oocyte-derived cytoplasm as a component of totipotency is outlined. Finally, the implications of twinning for our understanding of totipotency are discussed. HighlightsInaccurate use of the term ''totipotent'' by scientists creates unnecessary ethical controversy. Public concern over producing embryos by reprogramming reflects confusion over totipotency. Twinning by blastocyst splitting does not provide scientific evidence for totipotency.What Is Totipotency?

show abstract

High glucose impairs osteogenic differentiation of embryonic stem cells via early diversion of beta‐catenin from Forkhead box O to T cell factor interaction

Dienelt

Keller

Nieden

2022

Birth Defects Research

Self Cite

View full text Add to dashboard Cite

Background Diabetes, which is characterized by an increase in blood glucose concentration, is accompanied by low bone turnover, increased fracture risk, and the formation of embryonic skeletal malformations. Yet, there are few studies elucidating the underlying alterations in signaling pathways leading to these osteogenic defects. We hypothesized here that bone formation deficiencies in a high glucose environment result from altered activity of beta‐catenin (CTNNB1), a key contributor to osteogenic differentiation, dysregulation of which has also been implicated in the development of diabetes. Methods To test this hypothesis, we used a previously established embryonic stem cell (ESC) model of differentiation that mimics the diabetic environment of the developing embryo. We differentiated murine ESCs within osteogenic‐inducing media containing either high (diabetic) or low (physiological) levels of D‐glucose and performed time course analyses to study the influence of high glucose on early and late bone cell differentiation. Results Endpoint measures for osteogenic differentiation were reduced in a glucose‐dependent manner and expression of precursor‐specific markers altered at multiple time points. Furthermore, transcriptional activity of the lymphoid enhancer factor (LEF)/T cell factor (TCF) transcription factors during precursor formation stages was significantly elevated while levels of CTNNB1 complexed with Forkhead box O 3a (FOXO3a) declined. Modulation of AKT, a known upstream regulator of both LEF/TCF and FOXO3a, as well as CTNNB1 rescued some of the reductions in osteogenic output seen in the high glucose condition. Conclusions Within our in vitro model, we found a clear involvement of LEF/TCF and FOXO3a signaling pathways in the regulation of osteogenic differentiation, which may account for the skeletal deficiencies found in newborns of diabetic mothers.

show abstract

NO–β-catenin crosstalk modulates primitive streak formation prior to embryonic stem cell osteogenic differentiation

Cited by 8 publications

References 1 publication

Exogenous nitric oxide enhances calcification in embryonic stem cell-derived osteogenic cultures

Exogenous nitric oxide enhances calcification in embryonic stem cell-derived osteogenic cultures

Totipotency: What It Is and What It Is Not

High glucose impairs osteogenic differentiation of embryonic stem cells via early diversion of beta‐catenin from Forkhead box O to T cell factor interaction

Contact Info

Product

Resources

About