Osteogenesis and angiogenesis induced by porous β-CaSiO3/PDLGA composite scaffold via activation of AMPK/ERK1/2 and PI3K/Akt pathways

Wang, Chen; Lin, Kaili; Chang, Jiang; Sun, Jiao

doi:10.1016/j.biomaterials.2012.09.021

Cited by 250 publications

(183 citation statements)

References 69 publications

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“…The ERK1/2 and Wnt signaling pathways are also involved in biomaterial-induced osteogenic differentiation. 19 Signaling by Janus kinase (JNK), a member of the MAPK family, activates cell death from hypoxia/reoxygenation condition in cultured ADSCs. 20,21 Apoptosis of ADSCs driven by miR10b and miR23b expression occurs via the p38 signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation

Kim¹,

Joe²,

Kim³

et al. 2015

IJN

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Background Silicon dioxide composites have been found to enhance the mechanical properties of scaffolds and to support growth of human adipose tissue-derived stem cells (hADSCs) both in vitro and in vivo. Silica (silicon dioxide alone) exists as differently sized particles when suspended in culture medium, but it is not clear whether particle size influences the beneficial effect of silicon dioxide on hADSCs. In this study, we examined the effect of different sized particles on growth and mitogen-activated protein kinase signaling in hADSCs. Methods Silica gel was prepared by a chemical reaction using hydrochloric acid and sodium silicate, washed, sterilized, and suspended in serum-free culture medium for 48 hours, and then sequentially filtered through a 0.22 μm filter (filtrate containing nanoparticles smaller than 220 nm; silica NPs). hADSCs were incubated with silica NPs or 3 μm silica microparticles (MPs), examined by transmission electron microscopy, and assayed for cell proliferation, apoptosis, and mitogen-activated protein kinase signaling. Results Eighty-nine percent of the silica NPs were around 50–120 nm in size. When hADSCs were treated with the study particles, silica NPs were observed in endocytosed vacuoles in the cytosol of hADSCs, but silica MPs showed no cell entry. Silica NPs increased the proliferation of hADSCs, but silica MPs had no significant effect in this regard. Instead, silica MPs induced slight apoptosis. Silica NPs increased phosphorylation of extracellular signal-related kinase (ERK)1/2, while silica MPs increased phosphorylation of p38. Silica NPs had no effect on phosphorylation of Janus kinase or p38. Pretreatment with PD98059, a MEK inhibitor, prevented the ERK1/2 phosphorylation and proliferation induced by silica NPs. Conclusion Scaffolds containing silicon dioxide for tissue engineering may enhance cell growth through ERK1/2 activation only when NPs around 50–120 nm in size are included, and single component silica-derived NPs could be useful for bioscaffolds in stem cell therapy.

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Section: Introductionmentioning

confidence: 99%

Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation

Kim¹,

Joe²,

Kim³

et al. 2015

IJN

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“…Previous studies have shown that NO activation was involved in porous β-CaSiO 3 /Poly-D,L-LactideGlycolide (PDLGA) composite scaffold-induced increased angiogenic activity of ECs. 11 Whether NO plays a role in the effect of HANPs on ECs is an interesting issue.…”

mentioning

confidence: 99%

“…ECs not only are implicated in angiogenesis but also serve as biological barrier, mediating removal of nanoparticles (NPs) to maintain body homeostasis. 10,11 Therefore, interactions of HANPs with ECs are one of the most important items to understand the bioactivity and biocompatibility of nano-HAP. A general consensus exists that a detailed understanding of the process and mechanisms underlying cellular NPs uptake is crucial for exploring the effects of nanomaterials on biological systems and evaluating their potential harm to organisms, which will promote a safer and more efficient application of nanomaterials in biomedical fields.…”

mentioning

confidence: 99%

Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway

Shi¹,

Zhou²,

Huang³

et al. 2017

IJN

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Nano-hydroxyapatite (nano-HAP) has been proposed as a better candidate for bone tissue engineering; however, the interactions of nano-HAP with endothelial cells are currently unclear. In this study, HAP nanoparticles (HANPs; 20 nm np20 and 80 nm np80) and micro-sized HAP particles (m-HAP; 12 μm) were employed to explore and characterize cellular internalization, subcellular distribution, effects of HANPs on endothelial cell function and underlying mechanisms using human umbilical vein endothelial cells (HUVECs) as an in vitro model. It was found that HANPs were able to accumulate in the cytoplasm, and both adhesion and uptake of the HANPs followed a function of time; compared to np80, more np20 had been uptaken at the end of the observation period. HANPs were mainly uptaken via clathrin- and caveolin-mediated endocytosis, while macropinocytosis was the main pathway for m-HAP uptake. Unexpectedly, exposure to HANPs suppressed the angiogenic ability of HUVECs in terms of cell viability, cell cycle, apoptosis response, migration and capillary-like tube formation. Strikingly, HANPs reduced the synthesis of nitric oxide (NO) in HUVECs, which was associated with the inhibition of phosphatidylinositol 3-kinase (PI3K) and phosphorylation of eNOS. These findings provide additional insights into specific biological responses as HANPs interface with endothelial cells.

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“…In fact, many other types of stem cells are affected by CS ions through known signaling pathways. For example, pFAK-MAPK-ERK/Akt signaling plays an important role in inducing CS-treated stem cells to express differentiation biomarkers such as ALP and Runx2 7,26,30,33,35,41,57,58 . The cells recognize the bioceramic materials and stimulate the phosphorylation of FAK, which in turn activates other protein kinases and accomplishes the biological effects 33 .…”

Section: Discussionmentioning

confidence: 99%

“…CS induces osteogenic differentiation and angiogenesis in various cell types, such as mouse mesenchymal stem cells (mMSCs) 27 , rat MSCs 29,30 , human MSCs 22,[31][32][33][34][35] , mouse embryonic osteoblasts MC3T3-E1 36 , osteoblasts [37][38][39] , human adipose tissue-derived stem cell (ASCs) 26,38,40 , human dental pulp cells (hDPCs) 33,41 , human orofacial mesenchymal stem cells (hOFMSC) 28 , and human umbilical vein endothelial cells (HUVECs) 30,35 . Thus, it is reasonably hypothesized that CS and its ionic extracts may have the potential to affect the growth and differentiation of embryonic-derived stem cells.…”

Section: Introductionmentioning

confidence: 99%

Bioactive calcium silicate extracts regulate the morphology and stemness of human embryonic stem cells at the initial stage

Zhang

Lü

et al. 2016

RSC Adv.

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Embryonic stem cells (ESCs) are undifferentiated cells that have the capacity to self-renew and differentiate into a variety of cells and provide cell sources for regenerative medicine or biological specimens for cytotoxicity tests. Calcium silicate (CS), a bioactive silicate ceramic, can stimulate the osteogenic differentiation of various types of stem cells, but its role in regulating the biological phenotypes of ESCs remains unclear. Here, the impact of CS on human ESCs was investigated using CS-supplemented medium. The cytotoxicity of CS to hESCs and its effects on apoptosis, growth, proliferation, and differentiation were quantified systematically. Morphological analysis of hESC colonies indicated that the bioactive ions released from CS have little cytotoxicity to hESCs at two CS concentrations. Immunofluorescence and flow cytometry analyses showed that apoptosis was time-independent at early or late stages of hESC growth. In contrast, CS ion extracts regulated hESC differentiation in a time-dependent manner: ESC stemness was preserved by enhancing Oct-4, Sox-2, and Nanog gene expression at day 3, while the cells tended to differentiate at day 6. Combined tests on gene and protein levels further indicated that hESCs tended to differentiate into mesoderm in the presence of CS ion extracts, especially at low CS concentrations. These results demonstrate the effects of CS extracts on hESC stemness and differentiation at the molecular and cellular levels, suggesting that CS-based biomaterials could serve as a potential regulator for ESCs in regenerative medicine.

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Osteogenesis and angiogenesis induced by porous β-CaSiO3/PDLGA composite scaffold via activation of AMPK/ERK1/2 and PI3K/Akt pathways

Cited by 250 publications

References 69 publications

Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation

Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation

Interaction of hydroxyapatite nanoparticles with endothelial cells: internalization and inhibition of angiogenesis in vitro through the PI3K/Akt pathway

Bioactive calcium silicate extracts regulate the morphology and stemness of human embryonic stem cells at the initial stage

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