Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways

Song, Frank M.; Wang, Yi; Jiang, Dawei; Wang, Tianchen; Zhang, Yinquan; Ma, Hui; Kang, Yifan

doi:10.1371/journal.pone.0165845

Cited by 38 publications

(32 citation statements)

References 42 publications

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“…Our results imply that FSS‐induced Runx‐2 expression may be independent of Erk1/2 signaling. The different mechanotransductal effect between Erk1/2 and Akt agreed with Song's and Watabe's study (Watabe et al, 2011; Song et al, 2016). The specific mechanism needs further research.…”

Section: Discussionsupporting

confidence: 89%

Fluid shear stress induces Runx‐2 expression via upregulation of PIEZO1 in MC3T3‐E1 cells

Song

Liu

et al. 2020

Cell Biology International

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Mechanically induced biological responses in bone cells involve a complex biophysical process. Although various mechanosensors have been identified, the precise mechanotransduction pathway remains poorly understood. PIEZO1 is a newly discovered mechanically activated ion channel in bone cells. This study aimed to explore the involvement of PIEZO1 in mechanical loading (fluid shear stress)‐induced signaling cascades that control osteogenesis. The results showed that fluid shear stress increased PIEZO1 expression in MC3T3‐E1 cells. The fluid shear stress elicited the key osteoblastic gene Runx‐2 expression; however, PIEZO1 silencing using small interference RNA blocked these effects. The AKT/GSK‐3β/β‐catenin pathway was activated in this process. PIEZO1 silencing impaired mechanically induced activation of the AKT/GSK‐3β/β‐catenin pathway. Therefore, the results demonstrated that MC3T3‐E1 osteoblasts required PIEZO1 to adapt to the external mechanical fluid shear stress, thereby inducing osteoblastic Runx‐2 gene expression, partly through the AKT/GSK‐3β/β‐catenin pathway.

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Section: Discussionsupporting

confidence: 89%

Fluid shear stress induces Runx‐2 expression via upregulation of PIEZO1 in MC3T3‐E1 cells

Song

Liu

et al. 2020

Cell Biology International

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“…We also monitored compound B's ability to affect other signaling pathways. The JNK pathway is known to be activated when the cell undergoes apoptosis or stress (25). Compound B did not significantly alter phosphorylation of JNK at the Thr183/Y185 activation site at 24 h in WBras1 or H2009 cells.…”

Section: Discussionmentioning

confidence: 87%

Akt Pathway Inhibition of the Solenopsin Analog, 2-Dodecylsulfanyl-1,-4,-5,-6-tetrahydropyrimidine

et al. 2019

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Background/Aim: The P13K/Akt signaling pathway is a growth-regulating cellular pathway that is constitutively activated in a variety of human cancers. In previous studies, we reported that a solenopsin analog, compound B (MU-06-SC-608-7), shows inhibitory effects on Akt phosphorylation at a key activation site, as well as on proliferation of tumorigenic cells at sub-micromolar concentrations. The purpose of this study was to evaluate the effect of compound B on downstream effectors of Akt kinase, phosphorylation of Akt at a second activation site, Akt kinase activity in vitro, tumorigenic cell viability and other signaling pathways. Materials and Methods: Western blot analyses were performed using WBras1 epithelial and H2009 human carcinoma cells and cell viability assays were performed on H2009 cells. In vitro Akt kinase assays were performed using a commercially available kit. Results: Compound B decreased the phosphorylation of Akt at the Thr308 activation site and key downstream effectors of Akt kinase, but did not directly inhibit Akt kinase. Substantial decreases in cell viability were observed at concentrations above 5 μM. No effect was seen on ERK or JNK pathways. Conclusion: The results earmark this compound for further studies as a potential targeted cancer therapy. 5329

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“…Mitochondrial‐dependent apoptotic pathway plays an important role in cell apoptosis, which involves pro‐apoptotic protein Bax and anti‐apoptotic protein Bcl‐2 . Caspase‐3 is an executioner of apoptosis and is cleaved into activated form during apoptosis . Bax and Bcl‐2 exert the opposite effects on the activation of caspase‐3 .…”

Section: Discussionmentioning

confidence: 99%

Targeting protein for Xenopus kinesin‐like protein 2 knockdown enhances radiation sensitivity of human lung squamous carcinoma cell

Yang

Gao

et al. 2017

Clin Exp Pharma Physio

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The targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been demonstrated to be associated with the tumourigenesis of many cancers. In the present study, we investigated the role and preliminary mechanism of TPX2 in the resistance of lung squamous carcinoma to radiation therapy. The results showed that SK-MES-1R and NCI-H226R cells were more resistant to X-ray irradiation than the parental cells (SK-MES-1 and NCI-H226). Moreover, TPX2 was upregulated in the radioresistant cells compared with the parental cells. TPX2 knockdown significantly decreased TPX2 expression in SK-MES-1 cells, while TPX2 overexpression increased TPX2 expression in NCI-H226 cells compared with the corresponding control cells. TPX2 knockdown enhanced the radiosensitivity of SK-MES-1 and promoted cell apoptosis following exposure to irradiation, whereas TPX2 overexpression decreased the radiosensitivity of NCI-H226 and inhibited cell apoptosis. In in vivo studies, the combination of TPX2 knockdown and irradiation significantly inhibited tumour growth, decreased tumour weight, downregulated TPX2 expression in tumour tissue and induced cell apoptosis in nude mice, while TPX2 overexpression exerted an opposite effect. Our results indicated that TPX2 was correlated with cell radioresistance and it might be served as a therapeutic target to enhance cell radiosensitivity in the radiation therapy of lung squamous carcinoma.

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Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K/Akt and JNK MAPK Signaling Pathways

Cited by 38 publications

References 42 publications

Fluid shear stress induces Runx‐2 expression via upregulation of PIEZO1 in MC3T3‐E1 cells

Fluid shear stress induces Runx‐2 expression via upregulation of PIEZO1 in MC3T3‐E1 cells

Akt Pathway Inhibition of the Solenopsin Analog, 2-Dodecylsulfanyl-1,-4,-5,-6-tetrahydropyrimidine

Targeting protein for Xenopus kinesin‐like protein 2 knockdown enhances radiation sensitivity of human lung squamous carcinoma cell

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