Mechanical Strain Regulates Osteoblast Proliferation through Integrin-Mediated ERK Activation

Yan, Yu-xian; Gong, Yuanwei; Guo, Yong; Lv, Qi; Guo, Chun; Zhuang, Yan; Zhang, Yuan; Li, Ruixin; Zhang, Xizheng

doi:10.1371/journal.pone.0035709

Cited by 111 publications

(87 citation statements)

References 57 publications

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“…Several recent studies have indicated that overloaded strain could lead to pathological bone modeling, remodelling, or microdamage that might result in fractures when they accumulated [21, 22]. Previous studies have shown the mechanical strain of 5000 µε inhibited MC3T3-E1 cell proliferation [23]. In this study, the overload osteoblast damage model was constructed by stimulating MC3T3-E1 cells with a four-point bending device.…”

Section: Discussionmentioning

confidence: 99%

Use of an Osteoblast Overload Damage Model to Probe the Effect of Icariin on the Proliferation, Differentiation and Mineralization of MC3T3-E1 Cells through the Wnt/β-Catenin Signalling Pathway

Liu

Huang

Hao

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mechanical loading plays an important role in the regulation of bone mass. However, bone cells are not always under physiological stress. In some cases, bone tissue is subjected to an overloaded mechanical environment. For example, a person who is weight training and a stevedore often experience bone pain, inflammation and other bone fatigue damage symptoms. Icariin is the major ingredient of Herba epimedii, which has been widely used for the treatment of bone injury in traditional Chinese medicine, but its mechanism remains unknown. The aim of this study was to probe the effect of icariin on the proliferation and differentiation of osteoblasts exposed to overload and to determine whether the Wnt/β-catenin signalling pathway is involved in the drug response in osteoblasts. Methods: Mouse MC3T3-E1 cells were exposed to mechanical tensile strain using a four- point bending device to create an overload damage model. An MTT assay was performed to determine the effects of icariin on MC3T3-E1 cell proliferation. The mRNA and protein levels of ALP, COL-I, OCN, RUNX2 and β-catenin were assessed using RT-PCR and immunoblotting. The protein levels of β-catenin in the MC3T3-E1 cells were also determined using fluorescence microscopy. The mineralization of osteoblasts was assessed using Alizarin Red S staining. Results: We found that icariin enhanced the proliferation of osteoblasts exposed to overload and promoted MC3T3-E1 cell differentiation and mineralization. Furthermore, the gene and protein expression levels of β-catenin and RUNX2 all increased with icariin treatment compared with those in the damage group. Conclusion: Our study suggested that icariin promotes proliferation and differentiation in osteoblasts exposed to overload. The effect of icariin on osteoblastic differentiation acted by activating the RUNX2 promoter and the Wnt/β- catenin pathway.

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Section: Discussionmentioning

confidence: 99%

Use of an Osteoblast Overload Damage Model to Probe the Effect of Icariin on the Proliferation, Differentiation and Mineralization of MC3T3-E1 Cells through the Wnt/β-Catenin Signalling Pathway

Liu

Huang

Hao

et al. 2017

Cell Physiol Biochem

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“…Since we know that RAS-ERK pathway is involved in mechanical signal transduction [28,44]. We asked what is the role of NF1 in osteoblast during mechanical stress.…”

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%

Mechanical Signaling in NF1 Osteoblast Cells

Bamaga¹,

McHugh²

2017

J Den Craniofac Res

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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.

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“…miRNAs also activate multiple signaling pathways. The mitogen-activated protein kinase (MAPK) signaling pathway plays an important role in the osteogenic differentiation of mesenchymal stem cells in response to mechanical strain [Yan et al, 2012]. The Wnt signaling pathway is required for the osteogenic response to mechanical loading [Tu et al, 2012].…”

Section: Discussionmentioning

confidence: 99%

Mechanical Force-Induced Specific MicroRNA Expression in Human Periodontal Ligament Stem Cells

Wei

Wang

Ding

et al. 2014

Cells Tissues Organs

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It remains unclear how the expression of microRNAs (miRNAs) in human periodontal ligament stem cells (PDLSCs) might respond to mechanical stretch. To investigate specific miRNA expression in stretched PDLSCs, we used a Flexcell® FX-5000™ tension system to achieve external mechanical stimulation. Then, a custom-designed microarray assay was performed to investigate and describe the genome-wide differential expression of miRNAs in normal and stretched PDLSCs. Finally, we implemented integrative miRNA target prediction and network analysis approaches to construct an interaction network of the key miRNAs and their putative targets. We found that stretching induced morphological changes and increased alkaline phosphatase (ALP) activity, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and bone sialoprotein (BSP) expression in PDLSCs. The microarray data showed that 53 miRNAs were differentially expressed with stretching. With an interaction network, we examined the connections between 10 selected key miRNAs and their putative target genes, which were related to mechanical force. The results from the interaction network provided a basis for postulating the functional roles of miRNAs in PDLSCs.

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Mechanical Strain Regulates Osteoblast Proliferation through Integrin-Mediated ERK Activation

Cited by 111 publications

References 57 publications

Use of an Osteoblast Overload Damage Model to Probe the Effect of Icariin on the Proliferation, Differentiation and Mineralization of MC3T3-E1 Cells through the Wnt/β-Catenin Signalling Pathway

Use of an Osteoblast Overload Damage Model to Probe the Effect of Icariin on the Proliferation, Differentiation and Mineralization of MC3T3-E1 Cells through the Wnt/β-Catenin Signalling Pathway

Mechanical Signaling in NF1 Osteoblast Cells

Mechanical Force-Induced Specific MicroRNA Expression in Human Periodontal Ligament Stem Cells

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