Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis

Kearney, E. M.; Farrell, Eric; Prendergast, Patrick J.; Campbell, Veronica A.

doi:10.1007/s10439-010-9979-4

Cited by 119 publications

(111 citation statements)

References 61 publications

Supporting

Mentioning

104

Contrasting

Unclassified

Order By: Relevance

“…Also we tested the downstream effects of stretching on mineralized matrix formation. It has been shown that mechanical stimulation leads to increased matrix deposition [32,47]. deposit less matrix when mechanically stimulated compared to non-stressed Nf1(ob-/-) cells.…”

Section: Resultsmentioning

confidence: 99%

“…In this model, the Nf1 gene has been knocked-out using the Cre-LoxP system under the control of 2.3 kb collagen1-alpha1 promoter (Col11), which is primarily expressed in osteoblast [23,25]. Our current view of the NF1 bone pathology, based on the analysis of osteoblast function, whether the imbalance of bone homeostasis and improper response of osteoblast cell to mechanical stress cause the NF1 skeletal manifestations [26][27][28][29][30][31][32][33][34][35].…”

Section: Signaling In Nf1 Osteoblast Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Mechanical Signaling in NF1 Osteoblast Cells

Bamaga¹,

McHugh²

2017

J Den Craniofac Res

View full text Add to dashboard Cite

Neurofibromatosis Type I (NF1) syndrome is characterized by neurofibromas and neural tumors but is also associated with skeletal abnormalities. The cellular pathophysiology of skeletal abnormalities in NF1 is not understood. These abnormalities result from constitutive active RAS and its downstream effectors, RASERK pathway, due to mutation of NF1 gene which converts active RAS-GTP into inactive RAS-GDP. In osteoblast cells, RAS-ERK pathway is involved in cell proliferation and differentiation and is also involved in mechanical signals transduction.In this study, we propose that Nf1 mutation in osteoblast cells will affect the response to mechanical stimulation through the RAS pathway. The Flexcell tension system was used to mechanically stimulate calvarial osteoblast precursor from conditional knockout mice, Nf1(ob-/-), and wild type calvarial osteoblast precursor cells, (WT. The protocol of cyclic mechanical strain was 2% to 4% elongation at 0.16 Hz (10 cycles per minute) for 24 h. Mechanically stimulated cells showed lower expression levels of the osteoblast marker gene, RUNX2, measured at 4 h and 8 h post-stretch. Mineralized matrix deposition, assessed by Alizarin red staining, was decreased in Nf1(ob-/-) compared to (WT) cells following mechanical stimulation. the Nf1(ob-/-) and WT osteoblast precursor cells were then treated with RAS inhibitor (FTI-277), for 4 h and 8 h. RUNX2 expression level was increased in Nf1(ob-/-) cells compared to non-treated cells. However, the opposite result was seen in (WT) cells. The FTI-277 treatment resulted in lower RUNX2 expression level and lower mineralized matrix deposition.This response of (WT) cells was normal. However, the Nf1(ob-/-) response showed that these cells although they have hyper-active RAS, but when it is exposed to stress, it loses its ability to express osteoblast markers or lay down mineralized matrix. Our results indicate that, the hyperactive RAS in NF1 mutant osteoblast will result in cells being stuck in proliferative state and unable to differentiate.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Signaling In Nf1 Osteoblast Cellsmentioning

confidence: 99%

Mechanical Signaling in NF1 Osteoblast Cells

Bamaga¹,

McHugh²

2017

J Den Craniofac Res

View full text Add to dashboard Cite

show abstract

“…As with other methods, tension is applied cyclically (typically 1 Hz) to induce changes within the cells, 51 using strain magnitude (5-10%) similar to compressive loading. 67,68 …”

Section: D Compressionmentioning

confidence: 99%

“…64,65 or (e) strain. 67,68 In vitro loading of bone-derived cells RM Delaine-Smith et al A summary of the mechanical stimuli described is provided in Table 1.…”

Section: D Models For Loading Osteocyte-osteoblast Coculturesmentioning

confidence: 99%

Preclinical models for in vitro mechanical loading of bone-derived cells

Delaine-Smith¹,

Javaheri²,

Edwards³

et al. 2015

BoneKEy Reports

View full text Add to dashboard Cite

It is well established that bone responds to mechanical stimuli whereby physical forces are translated into chemical signals between cells, via mechanotransduction. It is difficult however to study the precise cellular and molecular responses using in vivo systems. In vitro loading models, which aim to replicate forces found within the bone microenvironment, make the underlying processes of mechanotransduction accessible to the researcher. Direct measurements in vivo and predictive modeling have been used to define these forces in normal physiological and pathological states. The types of mechanical stimuli present in the bone include vibration, fluid shear, substrate deformation and compressive loading, which can all be applied in vitro to monolayer and three-dimensional (3D) cultures. In monolayer, vibration can be readily applied to cultures via a low-magnitude, high-frequency loading rig. Fluid shear can be applied to cultures in multiwell plates via a simple rocking platform to engender gravitational fluid movement or via a pump to cells attached to a slide within a parallel-plate flow chamber, which may be micropatterned for use with osteocytes. Substrate strain can be applied via the vacuum-driven FlexCell system or via a four-point loading jig. 3D cultures better replicate the bone microenvironment and can also be subjected to the same forms of mechanical stimuli as monolayer, including vibration, fluid shear via perfusion flow, strain or compression. 3D cocultures that more closely replicate the bone microenvironment can be used to study the collective response of several cell types to loading. This technical review summarizes the methods for applying mechanical stimuli to bone cells in vitro.

show abstract

“…ASCs secrete osteoinductive growth factors, which may contribute to bone formation by recruiting host bone-forming cells or stimulating angiogenesis when implanted in vivo (Hao et al 2010;Scherberich et al 2010). Stretch-activated cation channels interpret mechanical strain in osteoblasts (Kearney et al 2010). One hypothesis is that forces acting on cells change protein conformation, exposing binding sites in a functionally relevant way (Teo et al 2010).…”

Section: Indirect and Chemical Mechanisms: Receptors Ion Channels Gmentioning

confidence: 99%

Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells

Salazar

Onodera

2012

Biophys Rev

View full text Add to dashboard Cite

Developing bone is subject to the control of a broad variety of influences in vivo. For bone repair applications, in vitro osteogenic assays are routinely used to test the responses of bone-forming cells to drugs, hormones, and biomaterials. Results of these assays are used to predict the behavior of bone-forming cells in vivo. Stem cell research has shown promise for enhancing bone repair. In vitro osteogenic assays to test the bone-forming response of stem cells typically use chemical solutions. Stem cell in vitro osteogenic assays often neglect important biophysical cues, such as the forces associated with regular weight-bearing exercise, which promote bone formation. Incorporating more biophysical cues that promote bone formation would improve in vitro osteogenic assays for stem cells. Improved in vitro osteogenic stimulation opens opportunities for "preconditioning" cells to differentiate towards the desired lineage. In this review, we explore the role of select biophysical factors-growth surfaces, tensile strain, fluid flow and electromagnetic stimulation-in promoting osteogenic differentiation of stem cells from human adipose. Emphasis is placed on the potential for physical microenvironment manipulation to translate tissue engineering and stem cell research into widespread clinical usage.

show abstract

Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis

Cited by 119 publications

References 61 publications

Mechanical Signaling in NF1 Osteoblast Cells

Mechanical Signaling in NF1 Osteoblast Cells

Preclinical models for in vitro mechanical loading of bone-derived cells

Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells

Contact Info

Product

Resources

About