Embryonic stem cell-derived osteocytes are capable of responding to mechanical oscillatory hydrostatic pressure

Ehnes, Devon; Price, Feodor D.; Shrive, Nigel G.; Hart, David A.; Rancourt, Derrick E.; Nieden, Nicole I. zur

doi:10.1016/j.jbiomech.2015.04.015

Cited by 8 publications

(10 citation statements)

References 73 publications

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“…We conclude this because by the end of week 3, Cbfa1 expression is beginning, followed by Ocn, both characteristic to an osteoblast-like state. In late week 4, Cbfa1 expression subsides and genes characteristic for osteocytes, such as CapG, and Sost are expressed (zur Nieden et al, 2003;Ding et al, 2012;Ehnes et al, 2015). These findings are an addition to previous reports that assign NO a role in early differentiation of ESCs.…”

Section: Discussionsupporting

confidence: 75%

“…Other studies purport that iNOS is not detectable in osteoblasts (Fox and Chow, 1998) unless the cells are induced with cytokines (MacPherson et al, 1999). In fact, we have previously shown that it is the iNOS mRNA that is up-regulated in mature osteogenic ESC cultures in response to a mechanical stimulus and not the eNOS mRNA (Ehnes et al, 2015). Together, our studies point to a potential role for eNOS during normal ESC differentiation and implicate iNOS in the bone-specific response to stresses, including those that involve mechanical cues, and provide another piece of evidence that osteogenesis from ESCs follows the signals and cues of in vivo osteogenesis and homeostasis underlining their promise as cell source for regenerative therapies.…”

Section: Discussionmentioning

confidence: 77%

“…Dissociation curves were generated post-run for analysis of amplicon species and n-fold gene regulation calculated according to the ΔΔC T method (Livak and Schmittgen, 2001) with Gapdh as the housekeeper gene. All primer sequences have been described previously (zur Nieden et al, 2003(zur Nieden et al, , 2005(zur Nieden et al, , 2007Ehnes et al, 2015).…”

Section: Gene Expression Analysismentioning

confidence: 99%

“…1B). At these later stages, ESC cultures express markers for maturing osteoblasts, such as Cbfa1, followed by destrin and macrophage-capping protein (CapG), which are normally attributed to osteocytes (Ehnes et al, 2015). Based on this observed up-regulation of NO levels in osteogenic cultures, a gene expression analysis was conducted to identify the synthase isoform possibly involved in the generation of NO.…”

Section: Temporal Activation Of No Signaling In Differentiating Escsmentioning

confidence: 99%

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

et al. 2015

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 77%

Section: Gene Expression Analysismentioning

confidence: 99%

Section: Temporal Activation Of No Signaling In Differentiating Escsmentioning

confidence: 99%

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

et al. 2015

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“…Other scaffolds that have been tested include decellularized osteoblast-derived extracellular matrix alone (26, 27) or on a PLGA scaffold (28), microcarriers (29), type I collagen gel (30), and hydroxyapatite/tricalcium phosphate (HA/TCP) (24, 31). Furthermore, investigators have tried to simulate mechanical loading in culture with approaches such as cyclic loading in a compression chamber (32) or culture on BioFlex plates (33). In the future a combination of these approaches will likely further enhance our ability to differentiate ES cells into osteoblasts.…”

Section: Directed Differentiation Of Es Cells Into Osteoblastsmentioning

confidence: 99%

Pluripotent Stem Cells and Skeletal Regeneration—Promise and Potential

2015

Curr Osteoporos Rep

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Bone is a regenerative tissue, capable of healing itself after fractures. However, some circumstances such as critical size defects, malformations, and tumor destruction may exceed the skeleton’s capacity for self-repair. In addition, bone mass and strength decline with age, leading to an increase in fragility fractures. Therefore the ability to generate large numbers of patient-specific osteoblasts would have enormous clinical implications for the treatment of skeletal defects and diseases. This review will highlight recent advances in the derivation of pluripotent stem cells, and in their directed differentiation towards bone-forming osteoblasts.

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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

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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.

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Embryonic stem cell-derived osteocytes are capable of responding to mechanical oscillatory hydrostatic pressure

Cited by 8 publications

References 73 publications

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

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

Pluripotent Stem Cells and Skeletal Regeneration—Promise and Potential

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

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