Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs

Wang, Qiwei; Chen, Bin; Cao, Meng; Sun, Jianfei; Wu, Hao; Zhao, Peng; Xing, Jing; Yang, Yan; Zhang, Xiquan; Ji, Min; Gu, Ning

doi:10.1016/j.biomaterials.2016.02.004

Cited by 227 publications

(186 citation statements)

References 57 publications

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“…Recent studies have suggested that the MAPK pathway is involved in the gene regulation mediated by osteoinductive biomaterials (Chen et al, ; Gong, Dong, Wang, Gao, & Chen, ; Wang, Chen, et al, ). Gong et al () investigated the effect of a novel nano‐sized bioactive glass (BG) on osteoblast‐like cells’ (MG‐63 cell) proliferation, osteogenic gene and protein expressions, matrix mineralization, and MAPK activation.…”

Section: Introductionmentioning

confidence: 99%

“…Blocking the ERK pathway induced a more obvious inhibitory effect on the genes’ normal expression and activation. In another study, systematic analysis by use of gene microarray assay and bioinformatics analysis demonstrated that MAPK signaling pathway was activated by Iron oxide nanoparticles treatment of human bone‐derived MSCs (hBMSCs), which resulted in the promotion of osteogenic differentiation in these cells (Wang, Chen, et al, ). Calcium phosphate (CaP) ceramics, with Osteoinductive properties, was also reported to be involved in the trigger of the intracellular MAPK signaling cascade to induce the osteogenic differentiation of MSCs (Chen et al, ).…”

Section: Introductionmentioning

confidence: 99%

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The roles of signaling pathways in bone repair and regeneration

Majidinia

Sadeghpour

Yousefi

2017

Journal Cellular Physiology

328

261

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Regenerative medicine has sparked interest in potential strategies for bone repair. Bone defects are widespread and could be caused by trauma, congenital malformations, infections, and surgery. Although bone has a large self-healing capacity, some defects or fractures are too big to regenerate. To regenerate bone structures which can be used for treatment of patients, bone growth must be induced by a number of bioactive implantable materials, cell types and intracellular, and extracellular molecular signaling pathways. Since mesenchymal stem cells (MSCs) and their differentiation during remodeling processes have important roles in bone regeneration, it is believed that understanding molecular signaling pathways involved is crucial to the development of bone implants, bone substitute materials, and cell-based scaffolds for bone regeneration. In this review, we briefly introduce concepts in fracture repair and regeneration following bone injuries, and then discuss the current clinical methods in bone regeneration. In the next section, we review the involvement of the various key signaling pathways in bone regeneration.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The roles of signaling pathways in bone repair and regeneration

Majidinia

Sadeghpour

Yousefi

2017

Journal Cellular Physiology

328

261

View full text Add to dashboard Cite

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“…In addition, assembled nanoparticles can exhibit some novel collective properties that freefloating nanoparticles do not. Different aggregation states of magnetic nanoparticles have shown various effects on the fates of stem cells [24,25]. Therefore, the endocytosis of both free-floating and assembled nanoparticles are worthy of further research.…”

Section: Introductionmentioning

confidence: 99%

Uptake of magnetic nanoparticles for adipose-derived stem cells with multiple passage numbers

et al. 2017

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With the increasingly promising role of nanomaterials in tissue engineering and regenerative medicine, the interaction between stem cells and nanoparticles has become a critical focus. The entry of nanoparticles into cells has become a primary issue for effectively regulating the subsequent safety and performance of nanomaterials in vivo. Although the influence of nanomaterials on endocytosis has been extensively studied, reports on the influence of stem cells are rare. Moreover, the effect of nanomaterials on stem cells is also dependent upon the action mode. Unfortunately, the interaction between stem cells and assembled nanoparticles is often neglected. In this paper, we explore for the first time the uptake of γ-Fe 2 O 3 nanoparticles by adipose-derived stem cells with different passage numbers. The results demonstrate that cellular viability decreases and cell senescence level increases with the extension of the passage number. We found the surface appearance of cellular membranes to become increasingly rough and uneven with increasing passage numbers. The iron content in the dissociative nanoparticles was also significantly reduced with increases in the passage number. However, we observed multiple-passaged stem cells cultured on assembled nanoparticles to have similarly low iron content levels. The mechanism may lie in the magnetic effect of γ-Fe 2 O 3 nanoparticles resulting from the field-directed assembly. The results of this work will facilitate the understanding and translation of nanomaterials in the clinical application of stem cells.

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“…Osteogenesis in human mesenchymal stem cells was improved by bioflavonoid treatment through the activation of c-Jun N-terminal kinase (JNK) and p38 MAPK pathways [37]. Inorganic nanoparticles such as those composed of gold or iron stimulate the osteogenesis of human periodontal ligament stem cells (PDLSCs) or human bone marrow stromal cells (BMSCs) in vitro via the p38 MAPK or extracellular signal-regulated kinase 1/2 (ERK1/2) activation [38,39]. Similar to our results, co-activation of NO, BMP2, and MAPK pathways are involved in osteoblast proliferation and differentiation downstream of phytoestrogeninduced osteogenesis [40].…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Effect of Inducible Nitric Oxide Synthase (iNOS)-Loaded Mineralized Nanoparticles on Embryonic Stem Cells

Lee¹,

Lee²,

Lee³

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study investigated the effect of inducible nitric oxide synthase-loaded mineralized nanoparticles (iNOS-MNPs) on the osteogenic differentiation of mouse embryonic stem cells (ESCs). Methods: We prepared iNOS-MNPs using an anionic block copolymer template-mediated calcium carbonate (CaCO₃) mineralization process in the presence of iNOS. iNOS-MNPs were spherical and had a narrow size distribution. iNOS was stably loaded within MNPs without denaturation. In order to confirm the successful introduction of iNOS-MNPs into the cytosol of ESCs, intracellular levels of nitric oxide (NO) was determined with a fluorometric analysis. A NO effector molecule, cyclic guanosine 3’,5’ monophosphate (cGMP) was also quantified with a competitive enzyme immunoassay. Cell viability in response to iNOS-MNP treatment was determined using the cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity assay, intracellular calcium quantification assay, and Alizarin red S staining for matrix mineralization were performed to investigate osteogenic differentiation of ESCs. The protein levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osterix (OSX) as osteogenic-related factors were also assessed by immunofluorescence staining and Western blot analysis. The complex pathways associated with iNOS-MNP-derived osteogenic differentiation of ESCs were evaluated by network-based analysis. Results: Cells with iNOS-MNPs displayed a significant increase in NO and cGMP concentration compared with the control group. When cells were exposed to iNOS-MNPs, there were no adverse effects on cell viability. Importantly, iNOS-MNP uptake promoted the osteogenic differentiation of ESCs. Using transcriptome profiling, we obtained 1,836 differentially-induced genes and performed functional enrichment analysis with ClueGO and KEGG. These analyses identified significantly enriched and interconnected molecular pathways such as protein kinase activity, estrogen receptor activity, bone morphogenetic protein (BMP) receptor binding, ligand-gated ion channel activity, and phosphatidylinositol 3-phosphate binding. Conclusion: These findings suggest that iNOS-MNPs can induce osteogenic differentiation in ESCs by integrating complex signaling pathways.

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Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs

Cited by 227 publications

References 57 publications

The roles of signaling pathways in bone repair and regeneration

The roles of signaling pathways in bone repair and regeneration

Uptake of magnetic nanoparticles for adipose-derived stem cells with multiple passage numbers

Osteogenic Effect of Inducible Nitric Oxide Synthase (iNOS)-Loaded Mineralized Nanoparticles on Embryonic Stem Cells

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