Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal-regulated kinase (ERK1/2) signaling pathway

Simmons, Craig A.; Matlis, Sean; Thornton, Amanda; Chen, Shaoqiong; Wang, Cun Yu; Mooney, David J.

doi:10.1016/s0021-9290(03)00110-6

Cited by 271 publications

(227 citation statements)

References 62 publications

Supporting

Mentioning

215

Contrasting

Unclassified

Order By: Relevance

“…In other cells, these FAK complexes are sensitive to a wide variety of extracellular stimuli beyond ECM binding, including glucocorticoids [36], peptide growth factors [37], and mechanical stress [38]. These same stimuli contribute to osteogenic differentiation on hMSC [5,39,40], and our data support the idea that FAK mediates this response.…”

Section: Discussionsupporting

confidence: 81%

Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells

Salasznyk

Klees

Williams

et al. 2007

Experimental Cell Research

265

225

View full text Add to dashboard Cite

The intracellular signaling events controlling human mesenchymal stem cell (hMSC) differentiation into osteoblasts are not entirely understood. We recently demonstrated that contact with extracellular matrix (ECM) proteins is sufficient to induce osteogenic differentiation of hMSC through an ERKdependent pathway. We hypothesized that FAK signaling pathways provide a link between activation of ERK 1/2 by ECM, and stimulate subsequent phosphorylation of the Runx2/Cbfa-1 transcription factor that controls osteogenic gene expression. We plated hMSC on purified collagen I (COLL-I) and vitronectin (VN) in the presence or absence of FAK-specific siRNA, and assayed for phosphorylation of Runx2/Cbfa-1 as well as expression of established osteogenic differentiation markers (bone sialoprotein-2, osteocalcin, alkaline phosphatase, calcium deposition, and spectroscopically determined mineral:matrix ratio). We found that siRNA treatment reduced FAK mRNA levels by >40% and decreased ECM-mediated phosphorylation of FAK Y397 and ERK 1/2. Serine phosphorylation of Runx2/Cbfa-1 was significantly reduced after 8 days in treated cells. Finally, FAK inhibition blocked osterix transcriptional activity and the osteogenic differentiation of hMSC, as assessed by lowered expression of osteogenic genes (RT-PCR), decreased alkaline phosphatase activity, greatly reduced calcium deposition, and a lower mineral:matrix ratio after 28 days in culture. These results suggest that FAK signaling plays an important role in regulating ECMinduced osteogenic differentiation of hMSC.

show abstract

Section: Discussionsupporting

confidence: 81%

Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells

Salasznyk

Klees

Williams

et al. 2007

Experimental Cell Research

265

225

View full text Add to dashboard Cite

show abstract

“…For instance Ku et al (2006) and Song et al (2007) show a positive correlation, while according to Simmons (2003), even small mechanical strain reduces the proliferation rate of mesenchymal cells. For now only the later results are included in this study.…”

Section: Appendix A: Parameters Of the Tissue Differentiation Modelmentioning

confidence: 96%

“…For now only the later results are included in this study. According to the study of Simmons (2003), the proliferation rate of the non-stimulated mesenchymal cells P m 0 can be estimated as 1.2 day −1 . Mechanical stimulation reduces this rate to around 0.5 day −1 .…”

Section: Appendix A: Parameters Of the Tissue Differentiation Modelmentioning

confidence: 99%

Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells

Andreykiv

Keulen

Prendergast

2007

Biomech Model Mechanobiol

View full text Add to dashboard Cite

Modelling the course of healing of a long bone subjected to loading has been the subject of several investigations. These have succeeded in predicting the differentiation of tissues in the callus in response to a static mechanical load and the diffusion of biological factors. In this paper an approach is presented which includes both mechanoregulation of tissue differentiation and the diffusion and proliferation of cell populations (mesenchymal stem cells, fibroblasts, chondrocytes, and osteoblasts). This is achieved in a three-dimensional poroelastic finite element model which, being poroelastic, can model the effect of the frequency of dynamic loading. Given the number of parameters involved in the simulation, a parameter variation study is reported, and final parameters are selected based on comparison with an in vivo experiment. The model predicts that asymmetric loading creates an asymmetric distribution of tissues in the callus, but only for high bending moments. Furthermore the frequency of loading is predicted to have an effect. In conclusion, a numerical algorithm is presented incorporating both mechanoregulation and evolution of cell populations, and it proves capable of predicting realistic difference in bone healing in a 3D fracture callus.

show abstract

“…Critical members of the MAPKs include extracellular regulated protein kinase (ERK)1/2, which is an essential molecule for mechanotransduction (13). Runx2 can be phosphorylated and activated by ERK1/2 pathways (14).…”

Section: Introductionmentioning

confidence: 99%

Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1/2-Runx2 signaling

et al. 2012

View full text Add to dashboard Cite

Abstract. Mechanical stimuli are responsible for bone remodeling during orthodontic tooth movement. The role of mechanical stimulation in the regulation of the fate of bone mesenchymal stem cells (BMSCs) is of interest in bone regeneration and tissue engineering applications. However, the signaling pathway involved in strain-induced biochemical events in BMSCs is not well established and can be controversial. This study investigated strain-induced proliferation and differentiation of BMSCs, as well as the mechanism of mechanotransduction. BMSCs were exposed to continuous mechanical strain (CMS) of 10% at 1 Hz. The results showed that CMS reduced the proliferation of BMSCs and stimulated osteogenic differentiation by activating Runx2, followed by increased alkaline phosphatase (ALP) activity and mRNA expression of osteogenesis-related genes (ALP, collagen type I and osteocalcin). Furthermore, the phosphorylation level of extracellular regulated protein kinase (ERK)1/2 increased significantly at the onset of strain. However, the presence of U0126, a selective inhibitor of ERK1/2, blocked the induction of Runx2 and subsequent osteogenic events. These findings demonstrate that CMS regulated Runx2 activation and favored osteoblast differentiation through activation of the ERK1/2 signaling pathway. These results will contribute to a better understanding of strain-induced bone remodeling and will form the basis for the correct choice of applied force in orthodontic treatment.

show abstract

Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal-regulated kinase (ERK1/2) signaling pathway

Cited by 271 publications

References 62 publications

Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells

Focal adhesion kinase signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells

Simulation of fracture healing incorporating mechanoregulation of tissue differentiation and dispersal/proliferation of cells

Osteogenic response of mesenchymal stem cells to continuous mechanical strain is dependent on ERK1/2-Runx2 signaling

Contact Info

Product

Resources

About