Mechanical strain promotes osteoblastic differentiation through integrin-β1-mediated β-catenin signaling

Yan, Yu-xian; Sun, Haoyang; Gong, Yuanwei; Yan, Zhixiong; Zhang, Xizheng; Guo, Yong; Wang, Yang

doi:10.3892/ijmm.2016.2636

Cited by 20 publications

(18 citation statements)

References 35 publications

(42 reference statements)

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“…It is known that the activity of osteocytes and osteoblasts are affected by mechanical stimulation (39,40). Therefore, we observed the influence of a mechanical load in vitro as demonstrated by periostin and semaphorin-3A levels in the osteoblast-like cell line, MC3T3-E1.…”

Section: Discussionmentioning

confidence: 74%

Influence of Mechanical Force on Bone Matrix Proteins in Ovariectomised Mice and Osteoblast-like MC3T3-E1 Cells

Zhang

Ishikawa

Tomoko

et al. 2017

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Section: Discussionmentioning

confidence: 74%

Influence of Mechanical Force on Bone Matrix Proteins in Ovariectomised Mice and Osteoblast-like MC3T3-E1 Cells

Zhang

Ishikawa

Tomoko

et al. 2017

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“…However, the molecular mechanism by which mechanical signals are transduced in osteoblasts remains unclear. Previous studies have indicated that the integrin/focal adhesion kinase pathway and calcium ion channels are involved in the signal transduction process ( 21 , 22 ). Robinson et al ( 23 ) demonstrated that target gene expression in the Wnt/β-catenin pathway was upregulated by the application of a four-point bending load to the long bones of low-density lipoprotein receptor related protein (Lrp) 5 transgenic mice, indicating that mechanical loading may activate the Wnt/β-catenin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Alterations in β‑catenin/E‑cadherin complex formation during the mechanotransduction of Saos‑2 osteoblastic cells

Zhang

Cui

et al. 2018

Mol Med Report

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Mechanical load application promotes bone formation, while reduced load leads to bone loss. However, the underlying mechanisms that regulate new bone formation are not fully understood. Wnt/β-catenin signaling has an important role in bone formation, bone growth and remodeling. The aim of the present study was to investigate whether mechanical stimuli regulated bone formation through the Wnt/β-catenin signaling pathway. Saos-2 osteoblastic cells were subjected to mechanical strain using a Flexcell strain loading system. The results demonstrated that 12% cyclical tensile stress significantly stimulated Saos-2 cell proliferation, increased the activity of alkaline phosphatase and promoted the formation of mineralized nodules, as determined by MTT and p-nitrophenyl phosphate assays and Alizarin Red S staining, respectively. Furthermore, western blot analysis demonstrated that, following mechanical strain, increased phosphorylation of glycogen synthase kinase-3β and nuclear β-catenin expression was observed in cells, compared with static control culture cells. Results of reporter gene and reverse transcription-polymerase chain reaction assays also demonstrated that mechanical strain significantly increased T-cell factor reporter gene activity and the mRNA expression of cyclooxygenase (COX)-2, cyclin D1, c-fos and c-Jun in Saos-2 cells. Co-immunoprecipitation analysis revealed that elongation mechanical strain activated Wnt/β-catenin signaling and reduced β-catenin and E-cadherin interaction in Saos-2 cells. In conclusion, the results of the current study indicate that mechanical strain may have an important role in the proliferation and differentiation of osteoblasts. The disassociation of the β-catenin/E-cadherin complex in the osteoblast membrane under stretch loading and the subsequent translocation of β-catenin into the nucleus may be an intrinsic mechanical signal transduction mechanism.

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“…Early osteoprogenitors can respond with the expansion of clonal proliferation and the enhancement of differentiation [9,10]. MC3T3-E1, a widely used preosteoblast lineage cell, is further promoted to differentiate and mineralize by mechanical stimuli, as evidenced by the increase in special gene markers [11,12]. In contrast, the absence of mechanical stimulation is able to inhibit the processes of MSC proliferation and osteogenic differentiation [13,14], increases osteoblast sensitivity to apoptosis and regression [15,16], and finally leads to a decreased rate of bone formation.…”

Section: Introductionmentioning

confidence: 99%

Targeted silencing of miRNA-132-3p expression rescues disuse osteopenia by promoting mesenchymal stem cell osteogenic differentiation and osteogenesis in mice

Zhang

Wang

et al. 2020

Stem Cell Res Ther

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Background: Skeletal unloading can induce severe disuse osteopenia that often occurs in spaceflight astronauts or in patients subjected to prolonged bed-rest or immobility. Previously, we revealed a mechano-sensitive factor, miRNA-132-3p, that is closely related to the osteoblast function. The aim of this study was to investigate whether miRNA-132-3p could be an effective target for treating disuse osteopenia. Methods: The 2D-clinostat device and the hindlimb-unloaded (HU) model were used to copy the mechanical unloading condition at the cellular and animal levels, respectively. Mimics or inhibitors of miRNA-132-3p were used to interfere with the expression of miRNA-132-3p in bone marrow-derived mesenchymal stem cells (BMSCs) in vitro for analyzing the effects on osteogenic differentiation. The special in vivo antagonists of miRNA-132-3p was delivered to the bone formation regions of HU mice for treating disuse osteopenia by a bone-targeted (AspSerSer) 6-cationic liposome system. The bone mass, microstructure, and strength of the hindlimb bone tissue were analyzed for evaluating the therapeutic effect in vivo. Results: miRNA-132-3p expression was declined under normal conditions and increased under gravitational mechanical unloading conditions during osteogenic differentiation of BMSCs in vitro. The upregulation of miRNA-132-3p expression resulted in the inhibition of osteogenic differentiation, whereas the downregulation of miRNA-132-3p expression enhanced osteogenic differentiation. The inhibition of miRNA-132-3p expression was able to attenuate the negative effects of mechanical unloading on BMSC osteogenic differentiation. Most importantly, the targeted silencing of miRNA-132-3p expression in the bone tissues could effectively preserve bone mass, microstructure, and strength by promoting osteogenic differentiation and osteogenesis in HU mice. Conclusion: The overexpression of miRNA-132-3p induced by mechanical unloading is disadvantageous for BMSC osteogenic differentiation and osteogenesis. Targeted silencing of miRNA-132-3p expression presents a potential therapeutic target for the prevention and treatment of disuse osteoporosis.

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Mechanical strain promotes osteoblastic differentiation through integrin-β1-mediated β-catenin signaling

Cited by 20 publications

References 35 publications

Influence of Mechanical Force on Bone Matrix Proteins in Ovariectomised Mice and Osteoblast-like MC3T3-E1 Cells

Influence of Mechanical Force on Bone Matrix Proteins in Ovariectomised Mice and Osteoblast-like MC3T3-E1 Cells

Alterations in β‑catenin/E‑cadherin complex formation during the mechanotransduction of Saos‑2 osteoblastic cells

Targeted silencing of miRNA-132-3p expression rescues disuse osteopenia by promoting mesenchymal stem cell osteogenic differentiation and osteogenesis in mice

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