Cyclic stretch enhances bone morphogenetic protein-2-induced osteoblastic differentiation through the inhibition of Hey1

Zeng, Zhaobin; Yin, Xiao; Zhang, Xiaodong; Jing, Da; Xue, Feng

doi:10.3892/ijmm.2015.2354

Cited by 27 publications

(28 citation statements)

References 36 publications

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“…A vibrational force that is perpendicularly induced at peak acceleration results in increased pro-osteogenic gene expression, even though smaller maximum strains \20 l strain were observed at 60 Hz and at 1.0 or 5.0 m/s 2 , respectively. This is in contrast with prior work describing enhanced osteoblast differentiation with 0.1 Hz of cyclic stretch (Zeng et al 2015). They found that a 10 % elongation (or a 1 9 10 5 l strain) was necessary to upregulate Runx2 gene expression.…”

Section: Discussioncontrasting

confidence: 55%

Vibrational stimulation induces osteoblast differentiation and the upregulation of osteogenic gene expression in vitro

2016

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Vibrational stimulation is an accepted non-invasive method used to improve bone remodeling. However, the underlying mechanisms of this phenomenon remain unclear. In this study, we developed a new vibration-loading system to apply vibrational stimulation to cells based on a previously reported in vivo study. We hypothesized that osteoblasts respond to vibrational strain by expressing osteogenic marker genes, such as alkaline-phosphatase (ALP), Runx2, and Osterix. To test our hypothesis, we developed a vibration-loading system to apply a precise vibrational force to an osteoblast culture on a silicone membrane. The system regulated frequency and acceleration of the vibration, and strain on the silicone membrane culture surface was measured using the strain gauge method. After vibrational stimulation, cellular gene expression was analyzed using real-time polymerase chain reaction. We obtained clear strain signals from the culture surface at vibrational ranges of 1.0-10 m/s 2 acceleration and frequencies of 30, 60, and 90 Hz, respectively. The strain increased in a linear fashion, depending on the acceleration magnitude. Vibrational stimulation also significantly upregulated expression of the osteogenic marker genes Runx2, Osterix, type I collagen, and ALP. In conclusion, we developed a new vibrationloading system that can precisely regulate frequency and acceleration, and we established the presence of dynamic cellular strain on a culture surface. Our findings suggest that vibrational stimulation may directly induce osteoblast differentiation.

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Section: Discussioncontrasting

confidence: 55%

Vibrational stimulation induces osteoblast differentiation and the upregulation of osteogenic gene expression in vitro

2016

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“…In contrast, in MC3T3 cells, cyclic tension resulted in Hey1 expression similar to that at baseline. However, BMP-2-induced Hey1 expression was attenuated (Zeng et al, 2015). Further, it has been shown in vitro that the application of static compressive force on hPDLs resulted in increased JAG1 expression (Kikuta et al, 2015), Moreover, Jagged1 and Notch2 protein expression were increased in PDL tissue on the compressive side of rat teeth subjected to orthodontic force (Kikuta et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Notch Signaling Participates in TGF‐β‐Induced SOST Expression Under Intermittent Compressive Stress

Manokawinchoke

Sumrejkanchanakij

Pavasant

et al. 2017

Journal Cellular Physiology

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Notch signaling is regulated by mechanical stimuli in various cell types. It has previously been reported that intermittent compressive stimuli enhanced sclerostin (SOST) expression in human periodontal ligament cells (hPDLs) by regulating transforming growth factor-β (TGF-β) expression. The aim of the present study was to determine the involvement of Notch signaling in the TGF-β-induced SOST expression in hPDLs. Cells were treated with intermittent compressive stress in a computer-controlled apparatus for 24 h. The mRNA and protein expression of the cells were determined by real-time polymerase chain reaction and Western blot analysis, respectively. In some experiments, the target signaling pathway was impeded by the addition of a TGF-β receptor kinase inhibitor (SB431542) or a γ-secretase inhibitor (DAPT). The results demonstrated that hPDLs under intermittent compressive stress exhibited significantly higher NOTCH2, NOTCH3, HES1, and HEY1 mRNA expression compared with control, indicating that mechanical stress induced Notch signaling. DAPT pretreatment markedly reduced the intermittent stress-induced SOST expression. The expression of NOTCH2, NOTCH3, HES1, and HEY1 mRNA under compressive stress was significantly reduced after pretreatment with SB431542, coinciding with a reduction in SOST expression. Recombinant human TGF-β1 enhanced SOST, Notch receptor, and target gene expression in hPDLs. Further, DAPT treatment attenuated rhTGF-β1-induced SOST expression. In summary, intermittent compressive stress regulates Notch receptor and target gene expression via the TGF-β signaling pathway. In addition, Notch signaling participates in TGF-β-induced SOST expression in hPDLs. J. Cell. Physiol. 232: 2221-2230, 2017. © 2016 Wiley Periodicals, Inc.

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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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Cyclic stretch enhances bone morphogenetic protein-2-induced osteoblastic differentiation through the inhibition of Hey1

Cited by 27 publications

References 36 publications

Vibrational stimulation induces osteoblast differentiation and the upregulation of osteogenic gene expression in vitro

Vibrational stimulation induces osteoblast differentiation and the upregulation of osteogenic gene expression in vitro

Notch Signaling Participates in TGF‐β‐Induced SOST Expression Under Intermittent Compressive Stress

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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