scholarly journals Calcium silicate enhances immunosuppressive function of MSCs to indirectly modulate the polarization of macrophages

2021 ◽  
Author(s):  
Haiyan Li ◽  
Wenrui Wang ◽  
Jiang Chang
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Calcium Silicate ◽  
Critical Role ◽  
Bone Tissue Regeneration ◽  
M2 Polarization ◽  
Marrow Mesenchymal Stem Cells ◽  
Underlying Mechanisms ◽  
Immunosuppressive Factors ◽  
Immunomodulatory Function

Abstract Bioactive silicate ceramics (BSCs) have been widely reported to be able to induce bone tissue regeneration, but the underlying mechanisms have not been fully elucidated. Previous studies have reported that ionic products of BSCs can promote bone regeneration by directly simulating osteogenic differentiation of MSCs and modulating the polarization of macrophages to create a favorable inflammation microenvironment for initiating bone regeneration cascades. However, the immunomodulatory ability of MSCs also plays a critical role in bone regeneration but the effects of BSCs on the immunomodulatory ability of MSCs have been rarely investigated. This study aims to investigate the effects of ionic products of BSCs on the immunoregulatory ability of MSCs to further understand the mechanism of BSCs enhancing bone regeneration. Results showed that ionic products of calcium silicate (CS), one of the representative BSCs, could enhance the immunosuppressive function of human bone marrow mesenchymal stem cells (HBMSCs) by up-regulating the expression of immunosuppressive factors in HBMSCs via NF-κB pathway. In addition, CS-activated HBMSCs showed stronger stimulatory effects on M2 polarization of macrophages than CS ionic products. Furthermore, the macrophages educated by CS-activated HBMSCs showed stronger stimulatory effects on the early osteogenic differentiation of HBMSCs than the ones regulated by CS ionic products. These results not only provide further understanding on the mechanism of BSCs enhancing bone regeneration but also suggest that it is critical to consider the effects of biomaterials on the immunomodulatory function of the tissue forming cells when the immunomodulatory function of biomaterials is investigated.

scholarly journals Accelerated Bone Regeneration by Adrenomedullin 2 Through Improving the Coupling of Osteogenesis and Angiogenesis via β-Catenin Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Feng Wang ◽  
Wenbo Wang ◽  
Lingchi Kong ◽  
Li Shi ◽  
Mengwei Wang ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Biological Activities ◽  
Angiogenic Potential ◽  
Hypoxic Injury ◽  
Peptide Family ◽  
Marrow Mesenchymal Stem Cells ◽  
Osteogenic Induction ◽  
Underlying Mechanisms

Both osteogenic differentiation and the pro-angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during distraction osteogenesis (DO). Adrenomedullin 2 (ADM2), an endogenous bioactive peptide belonging to the calcitonin gene-related peptide family, exhibits various biological activities associated with the inhibition of inflammation and the attenuation of ischemic-hypoxic injury. However, the effects and underlying mechanisms of ADM2 in osteogenic differentiation and the pro-angiogenic potential of BMSCs, along with bone regeneration, remain poorly understood. In the present study, we found that osteogenic induction enhanced the pro-angiogenic potential of BMSCs, and ADM2 treatment further improved the osteogenic differentiation and pro-angiogenic potential of BMSCs. Moreover, the accumulation and activation of β-catenin, which is mediated by the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the activation of protein kinase B (AKT), have been shown to contribute to the effects of ADM2 on BMSCs. In vivo, ADM2 accelerated vessel expansion and bone regeneration, as revealed by improved radiological and histological manifestations and the biomechanical parameters in a rat DO model. Based on the present results, we concluded that ADM2 accelerates bone regeneration during DO by enhancing the osteogenic differentiation and pro-angiogenic potential of BMSCs, partly through the NF-κB/β-catenin and AKT/β-catenin pathways. Moreover, these findings imply that BMSC-mediated coupling of osteogenesis and angiogenesis may be a promising therapeutic strategy for DO patients.

scholarly journals 3D-Printed Bioactive Calcium Silicate/Poly-ε-Caprolactone Bioscaffolds Modified with Biomimetic Extracellular Matrices for Bone Regeneration

2019 ◽  
Vol 20 (4) ◽  
pp. 942 ◽  
Author(s):  
Yuan-Haw Wu ◽  
Yung-Cheng Chiu ◽  
Yen-Hong Lin ◽  
Chia-Che Ho ◽  
Ming-You Shie ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Calcium Silicate ◽  
Interleukin 1 ◽  
Orthopedic Implants ◽  
Cellular Adhesion ◽  
Bone Tissue Regeneration ◽  
Necrosis Factor Alpha ◽  
Mg63 Cells ◽  
3D Printed

Currently, clinically available orthopedic implants are extremely biocompatible but they lack specific biological characteristics that allow for further interaction with surrounding tissues. The extracellular matrix (ECM)-coated scaffolds have received considerable interest for bone regeneration due to their ability in upregulating regenerative cellular behaviors. This study delves into the designing and fabrication of three-dimensional (3D)-printed scaffolds that were made out of calcium silicate (CS), polycaprolactone (PCL), and decellularized ECM (dECM) from MG63 cells, generating a promising bone tissue engineering strategy that revolves around the concept of enhancing osteogenesis by creating an osteoinductive microenvironment with osteogenesis-promoting dECM. We cultured MG63 on scaffolds to obtain a dECM-coated CS/PCL scaffold and further studied the biological performance of the dECM hybrid scaffolds. The results indicated that the dECM-coated CS/PCL scaffolds exhibited excellent biocompatibility and effectively enhanced cellular adhesion, proliferation, and differentiation of human Wharton’s Jelly mesenchymal stem cells by increasing the expression of osteogenic-related genes. They also presented anti-inflammatory characteristics by showing a decrease in the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Histological analysis of in vivo experiments presented excellent bone regenerative capabilities of the dECM-coated scaffold. Overall, our work presented a promising technique for producing bioscaffolds that can augment bone tissue regeneration in numerous aspects.

scholarly journals TNF-α-induced NF-κB activation upregulates microRNA-150-3p and inhibits osteogenesis of mesenchymal stem cells by targeting β-catenin

Open Biology ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 150258 ◽  
Author(s):  
Nan Wang ◽  
Zubin Zhou ◽  
Tianyi Wu ◽  
Wei Liu ◽  
Peipei Yin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Cells ◽  
Bone Diseases ◽  
Cytokine Activation ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells ◽  
Underlying Mechanisms

Although systemic or local inflammation, commonly featured by cytokine activation, is implicated in patients with bone loss, the underlying mechanisms are still elusive. As microRNAs (miR), a class of small non-coding RNAs involved in essential physiological processes, have been found in bone cells, we aimed to investigate the role of miR for modulating osteogenesis in inflammatory milieu using human bone marrow mesenchymal stem cells (hBM-MSCs). Induced by proinflammatory cytokine TNF-α, miR-150-3p was identified as a key player in suppressing osteogenic differentiation through downregulating β-catenin, a transcriptional co-activator promoting bone formation. TNF-α treatment increased the levels of miR-150-3p, which directly targeted the 3′-UTR of β-catenin mRNA and in turn repressed its expression. In addition, we observed that miR-150-3p expression was increased by TNF-α via IKK-dependent NF-κB signalling. There are three putative NF-κB binding sites in the promoter region of miR-150, and we identified −686 region as the major NF-κB binding site for stimulation of miR-150 expression by TNF-α. Finally, the osteogenic differentiation of hBM-MSCs was inhibited by either miR-150-3p overexpression or TNF-α treatment, which was prevented by anti-miR-150-3p oligonucleotides. Taken together, our data suggested that miR-150-3p integrated inflammation signalling and osteogenic differentiation and may contribute to the inhibition effects of inflammation on bone formation, thus expanding the pathophysiological functions of microRNAs in bone diseases.

scholarly journals The Critical Role of Long Noncoding RNA in Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoling Qiu ◽  
Bo Jia ◽  
Xiang Sun ◽  
Weitao Hu ◽  
Hongxing Chu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Critical Role ◽  
Human Bone ◽  
Differentially Expressed ◽  
Human Bone Marrow ◽  
Marrow Mesenchymal Stem Cells

Objective. Long noncoding RNAs (lncRNAs) have been demonstrated to regulate many biological processes including differentiation. However, their role in osteogenic differentiation was poorly known. Materials and Methods. In this study, we first globally profiled the differentially expressed lncRNAs and mRNAs during osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs). Bioinformatics analysis was performed to further analyze these significantly changed molecules. Then the role of lncRNA ENST00000502125.2 in the osteogenic differentiation was determined. Results. A number of lncRNAs and mRNAs were significantly differentially expressed during hBMMSC osteogenic differentiation. Among them, 433 lncRNAs and 956 mRNAs were continuously upregulated, while 232 lncRNAs and 229 mRNAs were continuously downregulated. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that carbohydrate derivative binding and complement and coagulation cascades were most correlated molecular function and pathway, respectively. Downregulation of lncRNA ENST00000502125.2 promoted the osteogenic differentiation of hBMMSCs, and opposite results were found when lncRNA ENST00000502125.2 was upregulated. Conclusions. lncRNAs play a critical role in the osteogenic differentiation of hBMMSCs and targeting lncRNA ENST00000502125.2 might be a promising strategy to promote osteogenic differentiation.

scholarly journals MicroRNA-378 Promotes Osteogenesis-Angiogenesis Coupling in BMMSCs for Potential Bone Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Bo Zhang ◽  
Yali Li ◽  
Yang Yu ◽  
Jinlong Zhao ◽  
Yangzhen Ou ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue Regeneration ◽  
Vascular Endothelial ◽  
Angiogenic Growth Factors ◽  
Alizarin Red ◽  
Gene Level ◽  
Marrow Mesenchymal Stem Cells ◽  
Exogenous Delivery ◽  
Endothelial Growth Factor ◽  
Potential Tool

Bone tissue regeneration was closely associated with osteogenesis and angiogenesis. The harmonious regulation of osteogenetic and angiogenic growth factors would enhance bone regeneration, while the imbalance of that would lead to local excessive bone formation or vascular mass due to exogenous delivery. Therefore, microRNA is believed to regulate multiple metabolism progress through endogenous signaling pathways on the gene level. In this work, we identified microRNA 378 as a positive regulator of osteogenesis and angiogenesis simultaneously and also observed an increase of microRNA 378 than control in human bone marrow mesenchymal stem cells (hBMMSCs) after osteoblast induction. Besides, osteogenetic and angiogenic gene expression increased simultaneously after overexpression of microRNA 378. Moreover, alizarin red staining and alkaline phosphatase (ALP) staining enhanced, and secretion of vascular endothelial growth factor (VEGF) increased. In this way, we believed miR378 was an ideal target to osteogenesis-angiogenesis coupling for bone regeneration, which provides a potential tool for the gene therapy of bone regeneration.

scholarly journals TRIM16 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating CHIP-Mediated Degradation of RUNX2

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Zhao ◽  
Qiaoli Zhai ◽  
Hong Liu ◽  
Xun Xi ◽  
Shuai Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Critical Role ◽  
Nodule Formation ◽  
Periodontal Ligament Stem Cells ◽  
Protein Levels ◽  
Periodontal Tissues ◽  
Short Hairpin Rnas

Bone regeneration is the ultimate goal of periodontal therapies, in which osteogenic differentiation of human periodontal ligament stem cells plays a critical role. The tripartite motif (TRIM)16, an E3 ubiquitin ligase, is downregulated in periodontal tissues of patients with periodontitis, while the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown. Firstly, we found that TRIM16 was increased throughout the osteogenic media induced differentiation of hPDLSCs. Then overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. TRIM16 significantly promoted alkaline phosphatase activity, mineralized nodule formation, and positively regulated the expression of osteo-specific markers RUNX2, COL1A1 and OCN except the mRNA of RUNX2. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. This study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which promoted the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.

scholarly journals Chaetocin Promotes Osteogenic Differentiation via Modulating Wnt/Beta-Catenin Signaling in Mesenchymal Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Youde Liang ◽  
Xin Liu ◽  
Ruiping Zhou ◽  
Dawei Song ◽  
Yi-Zhou Jiang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Bone Tissue Regeneration ◽  
Beta Catenin ◽  
Osteogenic Induction

Mesenchymal stemXin cells (MSCs) are a great cell source for bone regeneration. Although combining MSCs with growth factors and scaffolds provides a useful clinical strategy for bone tissue engineering, the efficiency of MSC osteogenic differentiation remains to be improved. Epigenetic modification is related to the differentiation ability of MSCs during osteogenic induction. In this study, we evaluate the effect of Chaetocin, an inhibitor of lysine-specific histone methyltransferases, on the differentiation of MSCs. We found that MSCs treated with Chaetocin demonstrated increased osteogenic ability and reduced adipogenic ability. The expression of osteogenic markers (Runx2 and OPN) was induced in MSCs by Chaetocin during osteogenic induction. Moveover, treatment of Chaetocin in MSCs improves Wnt/β-catenin signaling pathways and its downstream targets. Finally, we showed increased bone formation of MSC and Wnt/β-catenin signaling activity by treatment of Chaetocin using in vivo bone formation assays. Our data uncovered a critical role of Chaetocin in MSC osteogenic differentiation and provide new insights into bone tissue regeneration and repair.

scholarly journals La-Doped mesoporous calcium silicate/chitosan scaffolds for bone tissue engineering

2019 ◽  
Vol 7 (4) ◽  
pp. 1565-1573 ◽  
Author(s):  
Xiao-Yuan Peng ◽  
Min Hu ◽  
Fang Liao ◽  
Fan Yang ◽  
Qin-Fei Ke ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Calcium Silicate ◽  
Chitosan Scaffolds ◽  
La Doped

La-MCS/CTS scaffolds promoted the proliferation and osteogenic differentiation of rBMSCs in vitro and bone regeneration in vivo.

scholarly journals K-Carrageenan Stimulates Pre-Osteoblast Proliferation and Osteogenic Differentiation: A Potential Factor for the Promotion of Bone Regeneration?

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6131
Author(s):  
Wei Cao ◽  
Jianfeng Jin ◽  
Gang Wu ◽  
Nathalie Bravenboer ◽  
Marco N. Helder ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Metabolic Activity ◽  
Fold Increase ◽  
Bone Tissue Regeneration ◽  
Osteogenic Potential ◽  
Maximum Effect ◽  
Osteoblast Proliferation ◽  
Matrix Mineralization ◽  
Osteoblast Adhesion

Current cell-based bone tissue regeneration strategies cannot cover large bone defects. K-carrageenan is a highly hydrophilic and biocompatible seaweed-derived sulfated polysaccharide, that has been proposed as a promising candidate for tissue engineering applications. Whether κ-carrageenan can be used to enhance bone regeneration is still unclear. In this study, we aimed to investigate whether κ-carrageenan has osteogenic potential by testing its effect on pre-osteoblast proliferation and osteogenic differentiation in vitro. Treatment with κ-carrageenan (0.5 and 2 mg/mL) increased both MC3T3-E1 pre-osteoblast adhesion and spreading at 1 h. K-carrageenan (0.125–2 mg/mL) dose-dependently increased pre-osteoblast proliferation and metabolic activity, with a maximum effect at 2 mg/mL at day three. K-carrageenan (0.5 and 2 mg/mL) increased osteogenic differentiation, as shown by enhanced alkaline phosphatase activity (1.8-fold increase at 2 mg/mL) at day four, and matrix mineralization (6.2-fold increase at 2 mg/mL) at day 21. K-carrageenan enhanced osteogenic gene expression (Opn, Dmp1, and Mepe) at day 14 and 21. In conclusion, κ-carrageenan promoted MC3T3-E1 pre-osteoblast adhesion and spreading, metabolic activity, proliferation, and osteogenic differentiation, suggesting that κ-carrageenan is a potential osteogenic inductive factor for clinical application to enhance bone regeneration.

In vitro and in vivo osteogenesis up-regulated by two-dimensional nanosheets through a macrophage-mediated pathway

2021 ◽  
Author(s):  
Haoming Liu ◽  
Gaojie Yang ◽  
Hao Yin ◽  
Zhenxing Wang ◽  
Chunyuan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Calcium Phosphate ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Two Dimensional ◽  
M2 Polarization

Two-dimensional calcium phosphate nanomaterials are able to stimulate in vitro osteogenic differentiation of stem cells and in vivo bone regeneration by inducing M2 polarization of macrophages, rather than manipulating stem cells’ fate directly.

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