scholarly journals Strontium-substituted sub-micron bioactive glasses inhibit ostoclastogenesis through suppression of RANKL-induced signaling pathway

2020 ◽  
Vol 7 (3) ◽  
pp. 303-311 ◽  
Author(s):  
Deqiu Huang ◽  
Fujian Zhao ◽  
Wendong Gao ◽  
Xiaofeng Chen ◽  
Zhouyi Guo ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Signaling Pathway ◽  
Bone Repair ◽  
Superior Performance ◽  
Bioactive Glasses ◽  
Repair Materials ◽  
Potential Impact ◽  
Bone Repair Materials

Abstract Strontium-substituted bioactive glass (Sr-BG) has shown superior performance in bone regeneration. Sr-BG-induced osteogenesis has been extensively studied; however, Sr-BG-mediated osteoclastogenesis and the underlying molecular mechanism remain unclear. It is recognized that the balance of osteogenesis and osteoclastogenesis is closely related to bone repair, and the receptor activators of nuclear factor kappaB ligand (RANKL) signaling pathway plays a key role of in the regulation of osteoclastogenesis. Herein, we studied the potential impact and underling mechanism of strontium-substituted sub-micron bioactive glass (Sr-SBG) on RANKL-induced osteoclast activation and differentiation in vitro. As expected, Sr-SBG inhibited RANKL-mediated osteoclastogenesis significantly with the experimental performance of decreased mature osteoclasts formation and downregulation of osteoclastogenesis-related gene expression. Furthermore, it was found that Sr-SBG might suppress osteoclastogenesis by the combined effect of strontium and silicon released through inhibition of RANKL-induced activation of p38 and NF-κB pathway. These results elaborated the effect of Sr-SBG-based materials on osteoclastogenesis through RANKL-induced downstream pathway and might represent a significant guidance for designing better bone repair materials.

scholarly journals Effect of Cu- and Zn-Doped Bioactive Glasses on the In Vitro Bioactivity, Mechanical and Degradation Behavior of Biodegradable PDLLA Scaffolds

Materials ◽  
2020 ◽  
Vol 13 (13) ◽  
pp. 2908 ◽  
Author(s):  
Julian Bejarano ◽  
Aldo R. Boccaccini ◽  
Cristian Covarrubias ◽  
Humberto Palza
Keyword(s):  
Bioactive Glass ◽  
Bone Repair ◽  
Apatite Formation ◽  
High Porosity ◽  
Degradation Behavior ◽  
Polymer Scaffolds ◽  
Bioactive Glasses ◽  
Salt Leaching ◽  
Compression Properties

Biodegradable polymer scaffolds filled with bioactive glass particles doped with therapeutic metal ions are a novel and promising strategy to repair critical-sized bone defects. In this study, scaffolds based on a poly (D, L-lactide acid) (PDLLA) matrix filled with un-doped and Cu-, Zn- and CuZn-doped bioactive glass particles were produced by freeze-drying and a salt-leaching method. The effects of the doping and content of the glass particles (10 and 30 wt.%) on the morphology, compression properties, apatite formation, and degradation behavior of the scaffolds were evaluated. The scaffolds presented high porosity (~93%) with pores ranged from 100 to 400 μm interconnected by smaller pores and this porosity was kept after the glass particles incorporation. The glass particles reinforced the polymer scaffolds with improvements as high as 130% in elastic moduli, and further promoted the apatite formation on the scaffold surface, both properties depending on the amount and type of filler. The bioactive glass particles boosted the scaffold degradation with the PDLLA/un-doped glass scaffold showing the highest rate, but still retaining structural and dimensional integrity. Our findings show that the incorporation of un-doped and metal-doped bioactive glasses increases the mechanical strength, promotes the bioactivity and modifies the degradation profile of the resulting polymer/glass scaffolds, making them better candidates for bone repair.

Detailed structure of a new bioactive glass composition for the design of bone repair materials

2017 ◽  
Vol 475 ◽  
pp. 10-14 ◽  
Author(s):  
Ailing Li ◽  
Huihui Ren ◽  
Yang Cui ◽  
Chao Wang ◽  
Xiaojuan Zhou ◽  
...  
Keyword(s):  
Bioactive Glass ◽  
Bone Repair ◽  
Glass Composition ◽  
Detailed Structure ◽  
Repair Materials ◽  
Bone Repair Materials

scholarly journals The Development of Biomimetic Spherical Hydroxyapatite/Polyamide 66 Biocomposites as Bone Repair Materials

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Xuesong Zhang ◽  
Ming Lu ◽  
Yan Wang ◽  
Xiaojing Su ◽  
Xuelian Zhang
Keyword(s):  
Bone Repair ◽  
Chemical Bonds ◽  
Polyamide 66 ◽  
Biomedical Material ◽  
Natural Bone ◽  
Repair Materials ◽  
Proliferation And Differentiation ◽  
Molecule Interactions ◽  
Bone Repair Materials

A novel biomedical material composed of spherical hydroxyapatite (s-HA) and polyamide 66 (PA) biocomposite (s-HA/PA) was prepared, and its composition, mechanical properties, and cytocompatibility were characterized and evaluated. The results showed that HA distributed uniformly in the s-HA/PA matrix. Strong molecule interactions and chemical bonds were presented between the s-HA and PA in the composites confirmed by IR and XRD. The composite had excellent compressive strength in the range between 95 and 132 MPa, close to that of natural bone.In vitroexperiments showed the s-HA/PA composite could improve cell growth, proliferation, and differentiation. Therefore, the developed s-HA/PA composites in this study might be used for tissue engineering and bone repair.

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

Material Properties of Strontium Doped Bioactive Glasses/Hydroxyapatite Composite and Its Mechanism of Promoting Bone Repair

2021 ◽  
Vol 11 (12) ◽  
pp. 2313-2320
Author(s):  
Jian Zhao ◽  
Wei Li ◽  
Xin Dong ◽  
Jiying Chen
Keyword(s):  
Bone Repair ◽  
Sol Gel ◽  
Precipitation Method ◽  
Dissolution Behavior ◽  
Immersion Method ◽  
Bioactive Glasses ◽  
Strontium Content ◽  
M2 Polarization ◽  
Good Ability

Based on bioactive glasses (BG) of 58S, sol–gel method is used to prepare strontium oxide substituted bioactive glasses (SrO-BG) with different strontium content. SrO-BG and nano hydroxyapatite (HAp) composite materials were synthesized using precipitation method. The phase composition and morphologies of the prepared materials were examined by x-ray diffraction (XRD) and scanning electron microscopy (SEM) techniques. The dissolution and bio-mineralization of SrO-BG and SrO-BG/HAp composites in SBF are investigated by immersion method. The effects of secretion components of macrophages regulated by strontium doped SrO-BG/HAp composites on the osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) are analyzed. The results demonstrate that the SrO-BG can inhibit the dissolution of BG. Different proportions of SrO-BG/HAp composites show good ability to induce HAp in SBF. The bio-mineralization ability of SrO-BG/HAp composites increases with the increase of SrO-BG content. The results of dissolution behavior and bio-mineralization of SrO-BG/HAp composite show that the dissolution rate of each ion can be controlled by adjusting the content of SrO-BG in the composite, and then the degradation rate can effectively be controlled. The results of in vitro experiments show that SrO-BG/HAp composites with 2%, 5% and 8% strontium content are more effective in promoting M2 polarization of macrophages than SrO-BG/HAp composites with 0% strontium content. Among them, 5% strontium doped SrO-BG/HAp has the strongest effect on M2 polarization of macrophages, and the secretion of macrophages regulated by 5% strontium doped SrO-BG/HAp composite is more conducive to bone repair.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

scholarly journals Has-miR-875-5p Inhibits Tumorigenesis by Targeting USF2 via TGF-β Signaling Pathway in Gastric Cancer

2021 ◽  
Author(s):  
Shenshuo Gao ◽  
Zhikai Zhang ◽  
Xubin Wang ◽  
Yan Ma ◽  
Chensheng Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Research Direction ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
New Research

Abstract Background: Gastric cancer (GC) is one of the most common malignancies, and more and more evdiences show that the pathogenesis is regulated by various miRNAs.In this study, we investigated the role of miR-875 in GC. Methods:The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA RT-PCR. The effect of miR-875-5p on GC proliferation was determined by CCK-8 proliferation assay and EDU assay. Migration and invasion were examined by transwell migration and invasion assay and wound healing assay. The interaction between miR-875-5p and its target gene USF2 was verified by a dual luciferase reporter assay. The effects of miR-875-5p in vivo were studied in xenograft nude mice models.Related proteins were detected by Western blot.Results:The results showed that miR-875-5p inhibited the proliferation, migration and invasion of gastric cancer cells in vitro, and inhibited tumorigenesis in vivo. USF2 proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracts the effects of miR-875-5p inhibitors.Overexpression of miR-875-5p can inhibit proliferation, migration, and invasion through the TGF-β signaling pathway by down-regulation of USF2 in GC, providing a new research direction for the diagnosis and targeted therapy of GC.Conclusions: MiR-875-5pcan inhibited the progression of GC by directly targeting USF2 and negatively regulating TGF-β signaling pathway.In the future, miR-875-5p is expected to be used as a potential therapeutic target for GC therapy.

scholarly journals YAP regulates porcine skin-derived stem cells self-renewal partly by repressing Wnt/β-catenin signaling pathway

2021 ◽  
Author(s):  
Hong-Chen Yan ◽  
Yu Sun ◽  
Ming-Yu Zhang ◽  
Shu-Er Zhang ◽  
Jia-Dong Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Adult Stem Cells ◽  
Self Renewal ◽  
Human Ascs ◽  
Regulation Mechanisms ◽  
Interfering Rna ◽  
Pluripotency Genes

Abstract Background Skin-derived stem cells (SDSCs) are a class of adult stem cells (ASCs) that have the ability to self-renew and differentiate. The regulation mechanisms involved in the differentiation of ASCs is a hot topic. Porcine models have close similarities to humans and porcine SDSCs (pSDSCs) offer an ideal in vitro model to investigate human ASCs. To date, studies concerning the role of yes-associated protein (YAP) in ASCs are limited, and the mechanism of its influence on self-renewal and differentiation of ASCs remain unclear. In this paper, we explore the link between the transcriptional regulator YAP and the fate of pSDSCs. Results We found that YAP promotes the pluripotent state of pSDSCs by maintaining the high expression of the pluripotency genes Sox2, Oct4. The overexpression of YAP prevented the differentiation of pSDSCs and the depletion of YAP by small interfering RNA (siRNAs) suppressed the self-renewal of pSDSCs. In addition, we found that YAP regulates the fate of pSDSCs through a mechanism related to the Wnt/β-catenin signaling pathway. When an activator of the Wnt/β-catenin signaling pathway, CHIR99021, was added to pSDSCs overexpressing YAP the ability of pSDSCs to differentiate was partially restored. Conversely, when XAV939 an inhibitor of Wnt/β-catenin signaling pathway, was added to YAP knockdown pSDSCs a higher self-renewal ability resulted. Conclusions our results suggested that, YAP and the Wnt/β-catenin signaling pathway interact to regulate the fate of pSDSCs.

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