Dexamethasone suppresses osteogenesis of osteoblast via the PI3K/Akt signaling pathway in vitro and in vivo

Pan, Jiming; Wu, Longguo; Cai, Jingjing; Wu, Liting; Liang, Min

doi:10.1080/10799893.2019.1625061

Cited by 44 publications

(38 citation statements)

References 27 publications

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“…It has been reported that PI3K/Akt was the upstream regulator of GLUT1 and played a key role in a wide range of cellular activities, such as the bone healing, osteoclast formation, endothelialization, and inflammation. 4,69 But the role of the PI3K/Akt pathway in the inflammation response of biomaterials is not clear. In this study, we used 740Y-P to activate the PI3K/Akt pathway of Ag@TiO2-NTs group, and the immunofluorescence staining ( Figure 6A), western-blot ( Figure 6B and C) and qPCR ( Figure 6D) indicated that the expression of p-Akt on Ag@TiO 2 -NTs was the lowest compared with the expression of Ti and TiO 2 -NTs groups.…”

Section: Ag@tio2-nts Suppress Pi3k/akt Pathwaymentioning

confidence: 99%

Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO2 Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy

Chen¹,

Guan²,

Ren³

et al. 2020

IJN

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Introduction: The bone regeneration of endosseous implanted biomaterials is often impaired by the host immune response, especially macrophage-related inflammation which plays an important role in the bone healing process. Thus, it is a promising strategy to design an osteo-immunomodulatory biomaterial to take advantage of the macrophage-related immune response and improve the osseointegration performance of the implant. Methods: In this study, we developed an antibacterial silver nanoparticle-loaded TiO 2 nanotubes (Ag@TiO 2-NTs) using an electrochemical anodization method to make the surface modification and investigated the influences of Ag@TiO 2-NTs on the macrophage polarization, osteo-immune microenvironment as well as its potential molecular mechanisms in vitro and in vivo. Results: The results showed that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions had the excellent ability to induce the macrophage polarization towards the M2 phenotype and create a suitable osteo-immune microenvironment in vitro, via inhibiting PI3K/Akt, suppressing the downstream effector GLUT1, and activating autophagy. Moreover, Ag@TiO 2-NTs surface could improve bone formation, suppress inflammation, and promote osteo-immune microenvironment compared to the TiO 2-NTs and polished Ti surfaces in vivo. These findings suggested that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions could not only inhibit the inflammation process but also promote the bone healing by inducing healing-associated M2 polarization. Discussion: Using this surface modification strategy to modulate the macrophage-related immune response, rather than prevent the host response, maybe a promising strategy for implant surgeries in the future.

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Section: Ag@tio2-nts Suppress Pi3k/akt Pathwaymentioning

confidence: 99%

Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO2 Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy

Chen¹,

Guan²,

Ren³

et al. 2020

IJN

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“…AA is known to increase collagen-1 secretion into the ECM [255], while DX induces Runx2 expression [256] and BGP provides a source of phosphate for mineralisation [254]. While there have been a few controversial discussions regarding the use of dexamethasone induced differentiation [257,258], it has been used in vitro as an osteogenic supplement since as early as 1985 [259,260].…”

Section: On the Differentiation Of Stem Cellsmentioning

confidence: 99%

Attachment and spatial organisation of human mesenchymal stem cells on poly(ethylene glycol) hydrogels

Chahal

Schweikle

Heyward

et al. 2018

Journal of the Mechanical Behavior of Biomedical Materials

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Strategies that enable hydrogel substrates to support cell attachment typically incorporate either entire extracellular matrix proteins or synthetic peptide fragments such as the RGD (arginine-glycine-aspartic acid) motif. Previous studies have carefully analysed how material characteristics can affect single cell morphologies. However, the influence of substrate stiffness and ligand presentation on the spatial organisation of human mesenchymal stem cells (hMSCs) have not yet been examined. In this study, we assessed how hMSCs organise themselves on soft (E = 7.4-11.2 kPa) and stiff (E = 27.3-36.8 kPa) poly(ethylene glycol) (PEG) hydrogels with varying concentrations of RGD (0.05-2.5 mM). Our results indicate that hMSCs seeded on soft hydrogels clustered with reduced cell attachment and spreading area, irrespective of RGD concentration and isoform. On stiff hydrogels, in contrast, cells spread with high spatial coverage for RGD concentrations of 0.5 mM or higher. In conclusion, we identified that an interplay of hydrogel stiffness and the availability of cell attachment motifs are important factors in regulating hMSC organisation on PEG hydrogels. Understanding how cells initially interact and colonise the surface of this material is a fundamental prerequisite for the design of controlled platforms for tissue engineering and mechanobiology studies.

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“…OP is a metabolic bone disorder that increases the risk of fracture [1]. Long-term and high-dose administration of Dex has been reported to cause osteoblast apoptosis, osteopenia, and osteonecrosis and promote osteoclast proliferation, leading to OP [16,17]. Therefore, Dex was used to induce OP in C57BL/6 mice in this study to investigate the effects of the TCM YSBGY on OP.…”

Section: Discussionmentioning

confidence: 99%

The Antiosteoporosis Effects of Yishen Bugu Ye Based on Its Regulation on the Differentiation of Osteoblast and Osteoclast

Zhang

Meng

et al. 2020

BioMed Research International

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Yishen Bugu Ye (YSBGY), a traditional Chinese medicine comprising 12 types of medicinal herbs, is often prescribed in China to increase bone strength. In this study, the antiosteoporotic effects of YSBGY were investigated in C57BL/6 mice afflicted with dexamethasone-(Dex-) induced osteoporosis (OP). The results showed that YSBGY reduced the interstitial edema in the liver and kidney of mice with Dex-induced OP. It also increased the number of trabecular bone elements and chondrocytes in the femur, promoted cortical bone thickness and trabecular bone density, and modulated the OP-related indexes in the femur and tibia of OP mice. It also increased the serum concentrations of type I collagen, osteocalcin, osteopontin, bone morphogenetic protein-2, bone morphogenetic protein receptor type 2, C-terminal telopeptide of type I collagen, and runt-related transcription factor-2 and reduced those of tartrate-resistant acid phosphatase 5 and nuclear factor of activated T cells in these mice, suggesting that it improved osteoblast differentiation and suppressed osteoclast differentiation. The anti-inflammatory effect of YSBGY was confirmed by the increase in the serum concentrations of interleukin-(IL-) 33 and the decrease in concentrations of IL-1, IL-7, and tumor necrosis factor-α in OP mice. Furthermore, YSBGY enhanced the serum concentrations of superoxide dismutase and catalase in these mice, indicating that it also exerted antioxidative effects. This is the first study to confirm the antiosteoporotic effects of YSBGY in mice with Dex-induced OP, and it showed that these effects may be related to the YSBGYinduced modulation of the osteoblast/osteoclast balance and serum concentrations of inflammatory factors. These results provide experimental evidence supporting the use of YSBGY for supporting bone formation in the clinical setting.

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Dexamethasone suppresses osteogenesis of osteoblast via the PI3K/Akt signaling pathway in vitro and in vivo

Cited by 44 publications

References 27 publications

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO<sub>2</sub> Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO<sub>2</sub> Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

Attachment and spatial organisation of human mesenchymal stem cells on poly(ethylene glycol) hydrogels

The Antiosteoporosis Effects of Yishen Bugu Ye Based on Its Regulation on the Differentiation of Osteoblast and Osteoclast

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