MicroRNA-223 Suppresses Osteoblast Differentiation by Inhibiting DHRS3

Background/Aims: In this study, we aimed to use bioinformatics tools to identify the specific miRNAs and mRNAs involved in osteogenic differentiation and to further explore the way in which miRNA regulates osteogenic differentiation. Methods: The microarray GSE80614, which includes data from 3 human mesenchymal stromal cells (hMSCs) and 3 hMSCs after 72 hours (hr) of osteogenic differentiation, was used to screen for differentially expressed mRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of these mRNAs were conducted using Gene Set Enrichment Analysis (GSEA). Then, the miRanda website was employed to detect the binding sites of DHRS3. In vitro experiments, including RT-PCR and western blotting, were used to detect miR-233 and DHRS3 expression levels 7 and 14 days (d) after the induction of osteogenic differentiation using human bone marrow-derived mesenchymal stem cells (hBMSCs). The target relationship between miR-223 and DHRS3 was confirmed by a dual luciferase assay. ALP (alkaline phosphatase) staining, ARS (Alizarin Red S) staining and western blotting (Runx2, OPN, OCN) were used to detect the level of osteogenic differentiation after transfection with miR-223 mimics and DHRS3 cDNA. Results: In this study, 127 mRNAs differentially expressed during osteogenic differentiation were identified in GSE80614. GO term and KEGG pathway enrichment analyses found that the retinol metabolism pathway was activated during osteogenic differentiation and that DHRS3, which is involved in the pathway, was upregulated. During osteogenic differentiation in hBMSCs, miR-223 was gradually downregulated, while DHRS3 was upregulated. After 14 days of osteogenic differentiation, ALP and ARS staining assay results showed strong ALP activity and extracellular matrix calcification with the inhibition of miR-223 or the overexpression of DHRS3. Furthermore, the expression levels of Runx2, OPN, and OCN were upregulated with the knockdown of miR-223 or the overexpression of DHRS3, while the simultaneous transfection of a miR-223 agomir and DHRS3 cDNA resulted in no significant difference from the negative control (NC) group. Conclusion: The inhibition of miR-223 promotes the osteogenic differentiation of hBMSCs via the upregulation of DHRS3.

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Gujin Dan is A Chinese Medicine Formulation That Stimulates Cell Proliferation And Differentiation By Controlling Multiple Genes Involved In MC3T3-E1 Cells

10.21203/rs.3.rs-1089993/v1 ◽

2021 ◽

Author(s):

Yu Zhou ◽

Chaozong Liu ◽

Zhenwei Zhou ◽

Xin Li ◽

Songchuan Su ◽

...

Keyword(s):

Cell Proliferation ◽

Chinese Medicine ◽

Expression Patterns ◽

Osteoclast Formation ◽

Alizarin Red ◽

Gene Markers ◽

Expression Levels ◽

Chinese Herbal ◽

Alkaline Phosphatase Staining ◽

Proliferation And Differentiation

Abstract Background: The development of Chinese medicine has been practised in China over a long period of time, and China has long used single medicines in various forms of decoction to treat illnesses, and later learned to combine several medicines to form formulas to enhance the effects of the medicines. The use of Chinese herbal medicines and formulas has played a pivotal role in the prevention and treatment of diseases in China since ancient times. The application of Chinese herbal preparations in the field of osteoporosis treatment has received widespread attention, and Gujin Dan（GJD） is one of the representative herbal formulas, however, the exact minute mechanism of its treatment of osteoporosis remains to be elucidated.Methods: In the study, we prepared an aqueous extract of GJD and measured the effect of different administration concentrations of GJD on cell proliferation by CCK-8 assay, and the effect of GJD on cell differentiation ability by Alizarin Red S Staining, Alkaline Phosphatase Staining and quantitative assay. Changes in gene expression patterns of MC3T3-E1 cells under GJD treatment were investigated by RNA-seq analysis and validation methods.Results: We demonstrate that GJD promotes the proliferation and differentiation of Mc3t3-e1 cells through the regulation of multiple functional genes. This was mainly achieved by regulating the expression levels of four categories of genes that promote the proliferation of Mc3t3-e1 cells or osteoblasts, inhibit apoptosis and autophagy, inhibit osteoclast formation and differentiation, and promote osteoblast differentiation. In addition, GJD slightly increased the expression levels of gene markers in osteoblasts. Conclusions: Our findings suggest that GJD promotes proliferation and differentiation of MC3T3-E1 cells and inhibits osteoclastogenesis and differentiation, as well as apoptosis and autophagy, through the synergistic interaction of various herbs and their active components in GJD. This study has significantly improved the current understanding of the molecular effects of GJD on MC3T3-E1 cells. This study also provides new ideas for possible strategies to further prevent and treat bone metabolism-related diseases using traditional Chinese medicinal preparations.

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Potential Markers of Tongue Tumor Progression Selected by cDNA Micro Array

International Journal of Immunopathology and Pharmacology ◽

10.1177/039463200501800311 ◽

2005 ◽

Vol 18 (3) ◽

pp. 513-524 ◽

Cited By ~ 35

Author(s):

F. Carinci ◽

L. Lo Muzio ◽

A. Piattelli ◽

C. Rubini ◽

F. Chiesa ◽

...

Keyword(s):

Tumor Progression ◽

Differentially Expressed ◽

Premalignant Lesions ◽

Cell Cycle Regulators ◽

Agglomerative Clustering ◽

Expression Levels ◽

Extracellular Matrix Components ◽

Significant Difference ◽

Malignant Lesions ◽

Tongue Tumor

Squamous cell carcinoma (SCC), the most frequent malignant tumor of the oral cavity, generally exhibits a poor prognosis and metastases are the main cause of death. This tumor often arises from pre-malignant lesions. To date, it is difficult to predict if and which pre-malignant lesions may progress into oral SCC using traditional methods. For these reasons, several studies are trying to identify markers useful in the progression of pre-malignant lesions and tumors. To define the genetic expression profile of tongue tumor progression we compared 9 dysplasias (DS), 8 tumors without metastasis (TWM), 11 metastasizing SCCs (MT) of the tongue, and a baseline of 11 normal tissues by using cDNA microarray containing 19.2 K clones. We initially applied hierarchical agglomerative clustering based on information from all 6026 clones. Results were obtained by performing a two steps analysis: a Significance Analysis of Microarray (SAM) and a Gene Ontology search. One hundred and five clones have statistically significant different expression levels (FDR <0.01) between DS and TWM, whereas 570 genes have statistically significant difference expression levels between TWM and MT (FDR <0.01) as detected by SAM. By filtering with FatiGo only 33 genes were differentially expressed in TWN, respect to DS, whereas 155 genes were differentially expressed in MT respect to TWM. We detected some genes which encode for oncogenes, transcription factors and cell cycle regulators as potential markers of DS progression. Examples are BAG4, PAX3 and CCNI, respectively. Among potential markers of metastases are some genes related to cell mobility (TSPAN-2 and SNTA1), intercellular adhesion (integrin alpha 7) or extracellular matrix components (ADAMTS2 and cathepsin O). Additionally, under-expressed genes encoded apoptosis-related proteins (PDCD4 and CASP4). In conclusion, we identified several genes differentially expressed in tumor progression which can potentially help in better classifying premalignant lesions and tongue SCCs.

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LINC01018 and SMIM25 sponged miR-182-5p in endometriosis revealed by the ceRNA network construction

International Journal of Immunopathology and Pharmacology ◽

10.1177/2058738420976309 ◽

2020 ◽

Vol 34 ◽

pp. 205873842097630

Author(s):

Li Jiang ◽

Mengmeng Zhang ◽

Sixue Wang ◽

Yuzhen Xiao ◽

Jingni Wu ◽

...

Keyword(s):

Messenger Rna ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Protein Protein Interaction ◽

Cerna Network ◽

Non Coding Rna ◽

Differentially Expressed Mirnas ◽

Long Non Coding Rna

The current study intended to explore the interaction of the long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) under the background of competitive endogenous RNA (ceRNA) network in endometriosis (EMs). The differentially expressed miRNAs (DEmiRs), differentially expressed lncRNA (DELs), and differentially expressed genes (DEGs) between EMs ectopic (EC) and eutopic (EU) endometrium based on three RNA-sequencing datasets (GSE105765, GSE121406, and GSE105764) were identified, which were used for the construction of ceRNA network. Then, DEGs in the ceRNA network were performed with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analysis. Besides, the DEmiRs in the ceRNA network were validated in GSE124010. And the target DELs and DEGs of verified DEmiRs were validated in GSE86534. The correlation of verified DEmiRs, DEGs, and DELs was explored. Moreover, gene set enrichment analysis (GSEA) was applied to investigate the function of verified DEmiRs, DEGs, and DELs. Overall, 1352 DEGs and 595 DELs from GSE105764, along with 27 overlapped DEmiRs between GSE105765 and GSE121406, were obtained. Subsequently, a ceRNA network, including 11 upregulated and 16 downregulated DEmiRs, 7 upregulated and 13 downregulated DELs, 48 upregulated and 46 downregulated DEGs, was constructed. The GO and KEGG pathway analysis showed that this ceRNA network probably was associated with inflammation-related pathways. Furthermore, hsa-miR-182-5p and its target DELs (LINC01018 and SMIM25) and DEGs (BNC2, CHL1, HMCN1, PRDM16) were successfully verified in the validation analysis. Besides, hsa-miR-182-5p was significantly negatively correlated with these target DELs and DEGs. The GSEA analysis implied that high expression of LINC01018, SMIM25, and CHL1, and low expression of hsa-miR-182-5p would activate inflammation-related pathways in endometriosis EU samples. LINC01018 and SMIM25 might sponge hsa-miR-182-5p to upregulate downstream genes such as CHL1 to promote the development of endometriosis.

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miR-138-5p knockdown promotes osteogenic differentiation through FOXC1 up-regulation in human bone mesenchymal stem cells

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0163 ◽

2020 ◽

Author(s):

Lan Zhang ◽

Yan Liu ◽

Bo Feng ◽

Li-Gong Liu ◽

Ying-Cai Zhou ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Flow Cytometric Analysis ◽

Human Bone ◽

Luciferase Assay ◽

Induction Medium ◽

Cell Surface Antigens ◽

Bone Mesenchymal Stem Cells ◽

Alizarin Red

This study aimed to certify the hypothesis that miR-138-5p is expected to reduced osteodifferentiation of human bone mesenchymal stem cells (hBMSCs) by FOXC1 down-regulation. hBMSCs were separated from bone marrow and osteogenic induction medium was added to stimulate osteogenic differentiation. Flow cytometric analysis was applied to evaluate the expression of cell surface antigens associated with hBMSCs, including CD29, CD44, CD90, CD45 and CD34. qRT-PCR assay and western blot assay were determined to measure the mRNA and protein expression of miR-138-5p, OCN, RUNX2, BSP, ALP and FOXC1. Alkaline phosphatase (ALP) staining assay and Alizarin Red Staining (ARS) assay were determined to validate the osteogenic differentiation. Luciferase assay was applied to test the interaction of miR-138-5p and FOXC1. We demonstrated miR-138-5p is downregulated in osteogenic differentiated hBMSCs. Besides, miR-138-5p overexpression diminished osteodifferentiated markers expression, ALP activity and ARS activity. Furthermore, we revealed that forkhead transcription factor C1 (FOXC1) was a downstream target gene of miR-138-5p and knockdown of miR-138-5p improved the osteogenesis differentiation of hBMSCs by upregulating FOXC1. miR-138-5p knockdown promoted osteogenic differentiation in hBMSCs via directly targeting FOXC1. This study suggested miR-138-5p may be a new target for hBMSCs osteogenic differentiation and the treatment of bone defects.

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An Inhibitory Role of Osthole in Rat MSCs Osteogenic Differentiation and Proliferation via Wnt/β-Catenin and Erk1/2-MAPK Pathways

Cellular Physiology and Biochemistry ◽

10.1159/000445590 ◽

2016 ◽

Vol 38 (6) ◽

pp. 2375-2388 ◽

Cited By ~ 12

Author(s):

Hongyang Hu ◽

Min Chen ◽

Guangzu Dai ◽

Guoqing Du ◽

Xuezong Wang ◽

...

Keyword(s):

Osteogenic Differentiation ◽

Signaling Pathways ◽

Western Blotting ◽

Underlying Mechanism ◽

Mapk Signaling ◽

Cell Counting ◽

Nuclear Antigen ◽

Dependent Manner ◽

Alizarin Red ◽

Mapk Signaling Pathways

Background/Aims: Bone marrow-derived mesenchymal stem cells (MSCs) are responsible for new bone formation during adulthood. Accumulating evidences showed that Osthole promotes the osteogenic differentiation in primary osteoblasts. The aim of this study was to investigate whether Osthole exhibits a potential to stimulate the osteogenic differentiation of MSCs and the underlying mechanism. Methods: MSCs were treated with a gradient concentration of Osthole (6.25 µM, 12.5 µM, and 25 µM). Cell proliferation was assessed by western blotting with the proliferating cell nuclear antigen (PCNA) and Cyclin D1 antibodies, fluorescence activated cell sorting (FACS), and cell counting kit 8 (CCK8). MSCs were cultured in osteogenesis-induced medium for one or two weeks. The osteogenic differentiation of MSCs was estimated by Alkaline Phosphatase (ALP) staining, Alizarin red staining, Calcium influx, and quantitative PCR (qPCR). The underlying mechanism of Osthole-induced osteogenesis was further evaluated by western blotting with antibodies in Wnt/β-catenin, PI3K/Akt, BMPs/smad1/5/8, and MAPK signaling pathways. Results: Osthole inhibited proliferation of rat MSCs in a dose-dependent manner. Osthole suppressed osteogenic differentiation of rat MSCs by down-regulating the activities of Wnt/β-catenin and Erk1/2-MAPK signaling. Conclusions: Osthole inhibits the proliferation and osteogenic differentiation of rat MSCs, which might be mediated through blocking the Wnt/β-catenin and Erk1/2-MAPK signaling pathways.

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Impaired Osteogenic Differentiation Of Mesenchymal Stem Cells Derived From Bone Marrow Of Patients With Low-Risk Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v122.21.1579.1579 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1579-1579

Author(s):

Chunkang Chang ◽

Chengming Fei ◽

Youshan Zhao ◽

Juan Guo ◽

Xiao Li

Keyword(s):

Alkaline Phosphatase ◽

Osteogenic Differentiation ◽

Lower Risk ◽

Conflicts Of Interest ◽

Osteoblastic Differentiation ◽

Differentiation Markers ◽

Alizarin Red ◽

Hematopoietic Microenvironment ◽

Alkaline Phosphatase Staining ◽

Osteogenic Induction

Abstract Background The pathogenesis of MDS has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. MSCs and osteoblasts are key components of the hematopoietic microenvironment. Studying osteoblastic differentiation of MSCs quantitatively may help to understand the pathogenesis of MDS. Methods 38 patients with MDS and 15 normal donors were investigated in this study. Osteoblastic differentiation assays were performed in 16 MDS cases and 8 controls. The expression of osteogenic differentiation markers were measured by real-time PCR. Alkaline phosphatase staining was performed with Alkaline Phosphatase staining kit after 3,7,14 days of incubation. ALP activity was assessed at 3, 7, and 10 days after osteogenic differentiation. Mineralization analysis was performed at 7, 14 and 21 days of osteogenic induction. The areas of mineralization were measured by Image-Pro Plus 6.0 software. Results Both MDS-MSCs and normal cells displayed same fibroblast-like morphology and similar antigen expression. The expression level of RUNX2 was significantly decreased in MSCs from MDS, compaired with normal controls, especially in lower-risk MDS. After osteogenic induction, lower-risk MDS showed lower alkaline phosphatase activity, less intense alizarin red S staining, and lower gene expression of osteogenic differentiation markers, however, higher-risk MDS was normal. Conclusions We concluded that impaired osteogenic differentiation of MSCs was seen mainly in patients with lower-risk MDS. It may contribute to the ineffective hamatopoiesis of MDS. Disclosures: No relevant conflicts of interest to declare.

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Prediction of molecular markers of bovine mastitis by meta-analysis of differentially expressed genes using combined p-value and robust rank aggregation

10.1101/2021.11.24.469841 ◽

2021 ◽

Author(s):

Anushri Umesh ◽

Praveen Kumar Guttula ◽

Mukesh Kumar Gupta

Keyword(s):

Molecular Markers ◽

Differentially Expressed Genes ◽

Meta Analysis ◽

Mirna Gene ◽

Bovine Mastitis ◽

Rank Aggregation ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

P Value ◽

Expression Levels

Bovine mastitis causes significant economic loss to the dairy industry by affecting milk quality and quantity. E.coli and S.aureus are the two common mastitis-causing bacteria among the consortia of mastitis pathogens, wherein E.coli is an opportunistic environmental pathogen, and S.aureus is a contagious pathogen. This study was designed to predict molecular markers of bovine mastitis by meta-analysis of differentially expressed genes (DEG) in E.coli or S.aureus infected mammary epithelial cells (MECs) using p-value combination and robust rank aggregation (RRA) methods. High throughput transcriptome of bovine (MECs, infected with E.coli or S.aureus, were analyzed, and correlation of z-scores were computed for the expression datasets to identify the lineage profile and functional ontology of DEGs. Key pathways enriched in infected MECs were deciphered by Gene Set Enrichment Analysis (GSEA), following which combined p-value and RRA were used to perform DEG meta-analysis to limit type I error in the analysis. The miRNA-Gene networks were then built to uncover potential molecular markers of mastitis. Lineage profiling of MECs showed that the gene expression levels were associated with mammary tissue lineage. The up-regulated genes were enriched in immune-related pathways whereas down-regulated genes influenced the cellular processes. GSEA analysis of DEGs deciphered the involvement of Toll-like receptor (TLR), and NF- Kappa B signalling pathway during infection. Comparison after meta-analysis yielded with genes ZC3H12A, RND1 and MAP3K8 having significant expression levels in both E.coli and S.aureus dataset and on evaluating miRNA-Gene network 7 pairs were common to both sets identifying them as potential molecular markers.

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Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/β-catenin pathway and prevents bone loss in an ovariectomized rat model

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02239-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ming Chen ◽

Hui Han ◽

Siqi Zhou ◽

Yinxian Wen ◽

Liaobin Chen

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Signaling Pathway ◽

Western Blotting ◽

Nuclear Translocation ◽

Osteoclast Differentiation ◽

Alizarin Red ◽

Marrow Mesenchymal Stem Cells

Abstract Background Osteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear. Methods BMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry. Results The results showed the function of 2.5–10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/β-catenin signaling pathway) was added to the Morusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in the rat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo. Conclusions This study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.

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LncRNA DANCR and miR-320a suppressed osteogenic differentiation in osteoporosis by directly inhibiting the Wnt/β-catenin signaling pathway

Experimental & Molecular Medicine ◽

10.1038/s12276-020-0475-0 ◽

2020 ◽

Vol 52 (8) ◽

pp. 1310-1325

Author(s):

Cheng-Gong Wang ◽

Yi-He Hu ◽

Shi-Long Su ◽

Da Zhong

Keyword(s):

Osteogenic Differentiation ◽

Signaling Pathway ◽

Morphological Changes ◽

Osteoporosis Treatment ◽

Inhibitory Effect ◽

Luciferase Assay ◽

Blue Staining ◽

Alcian Blue Staining ◽

Alizarin Red

Abstract Our study aimed to determine how lncRNA DANCR, miR-320a, and CTNNB1 interact with each other and regulate osteogenic differentiation in osteoporosis. qRT-PCR and western blotting were performed to determine the expression of DANCR, miR-320a, CTNNB1, and the osteoporosis- or Wnt/β-catenin pathway-related markers T-cell factor 1 (TCF-1), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Interactions between CTNNB1, DANCR, and miR-320a were predicted by bioinformatics approaches and validated using a luciferase assay. Osteoblastic phenotypes were evaluated by ALP staining, ALP activity assay and Alizarin Red staining. The bilateral ovariectomy method was used to establish an in vivo osteoporosis model. Bone morphological changes were examined using hematoxylin and eosin (H&E) and Alcian Blue staining. The expression levels of DANCR and miR-320a in BMSCs derived from osteoporosis patients were upregulated, whereas CTNNB1 expression was downregulated compared with that in healthy controls. Importantly, we demonstrated that miR-320a and DANCR acted independently from each other and both inhibited CTNNB1 expression, whereas the inhibitory effect was additive when miR-320a and DANCR were cooverexpressed. Moreover, we found that DANCR overexpression largely abrogated the effect of the miR-320a inhibitor on CTNNB1 expression and the Wnt/β-catenin signaling pathway in BMSCs during osteogenic differentiation. We further confirmed the results above in BMSCs derived from an osteoporosis animal model. Taken together, our findings revealed that DANCR and miR-320a regulated the Wnt/β-catenin signaling pathway during osteogenic differentiation in osteoporosis through CTNNB1 inhibition. Our results highlight the potential value of DANCR and miR-320a as promising therapeutic targets for osteoporosis treatment.

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rBMSC osteogenic differentiation enhanced by graphene quantum dots loaded with immunomodulatory layered double hydroxide nanoparticles

Biomedical Materials ◽

10.1088/1748-605x/ac4324 ◽

2021 ◽

Author(s):

Zhaojie Wang ◽

Huiyi Yang ◽

Yuxin Bai ◽

Liming Cheng ◽

Rongrong Zhu

Keyword(s):

Quantum Dots ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Layered Double Hydroxide ◽

Therapeutic Potential ◽

Graphene Quantum Dots ◽

Allogeneic Bone ◽

Alizarin Red ◽

Alkaline Phosphatase Staining ◽

Double Hydroxide

Abstract Bone tissue defects caused by disease, trauma, aging or genetic factors emerged as one of the main factors that endanger human health. At present, advanced development of bone tissue engineering and regenerative medicine focused on the biomaterials regulated stem cell for responsive differentiation. In vivo transplantation of allogeneic bone materials has the needs of both osteogenic and immune regulation function. In this study, we utilized the extensively proved biocompatible layered double hydroxide (LDH) nanoparticles as the nanocarrier of graphene quantum dots (GQD), the functional loading was validated by characteristics analysis of scanning electron microscopy, surface zeta potential, X-ray diffraction and fourier transform infrared spectroscopy. Further, we investigated the cellular uptake of nanoparticles in rat bone marrow derived mesenchymal stem cells, the significant enhanced endocytosis was occurred in LDH-GQD treated groups. The enhanced osteogenic differentiation abilities of LDH-GQD were systematically investigated through alkaline phosphatase staining, alizarin red staining and qPCR analysis. In addition, the anti-inflammatory regulation of LDH facilitated the phenotypic transition of macrophage in LDH-GQD nanocomposites. Overall, the successful construction and functional validation of nanomaterials in this study will provide clinical therapeutic potential in bone defects regeneration.

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