The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

Feng, Qianyun; Zheng, Shusen; Zheng, Jia

doi:10.1042/bsr20180453

Cited by 79 publications

(66 citation statements)

References 72 publications

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“…Recent evidence indicates that, among the mechanisms by which naturally occurring compounds, such as resveratrol and anthocyanin, impact bone cell activities, the bone epigenome exerts a fundamental role [19]. The epigenetic regulation of osteoblast activity refers to the mechanisms that impact gene expressions such as post-translational histone modifications, miRNA-mediated post-transcriptional regulation, and DNA methylation [41,42]. In the present study, we examined the possible epigenetic mechanisms by which δTT exerts its positive effects on MC3T3-E1 cells.…”

Section: Discussionmentioning

confidence: 99%

Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration

Casati

Pagani

Maggi

et al. 2020

IJMS

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Bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, indicating that stimulation of osteoblast migration could be a promising osteoanabolic strategy. We showed that purified δ-tocotrienol (δ-TT, 10 μg/mL), isolated from commercial palm oil (Elaeis guineensis) fraction, stimulates the migration of both MC3T3-E1 osteoblast-like cells and primary human bone marrow mesenchymal stem cells (BMSC) as detected by wound healing assay or Boyden chamber assay respectively. The ability of δ-TT to promote MC3T3-E1 cells migration is dependent on Akt phosphorylation detected by Western blotting and involves Wnt/β-catenin signalling pathway activation. In fact, δ-TT increased β-catenin transcriptional activity, measured using a Nano luciferase assay and pretreatment with procaine (2 µM), an inhibitor of the Wnt/β-catenin signalling pathway, reducing the wound healing activity of δ-TT on MC3T3-E1 cells. Moreover, δ-TT treatment increased the expression of β-catenin specific target genes, such as Osteocalcin and Bone Morphogenetic Protein-2, involved in osteoblast differentiation and migration, and increased alkaline phosphatase and collagen content, osteoblast differentiation markers. The ability of δ-TT to enhance the recruitment of BMSC, and to promote MC3T3-E1 differentiation and migratory behavior, indicates that δ-TT could be considered a promising natural anabolic compound.

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Section: Discussionmentioning

confidence: 99%

Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration

Casati

Pagani

Maggi

et al. 2020

IJMS

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“…Another class of molecules useful for conjugation with biomimetic materials is represented by miRNAs because of their known involvement in different diseases (for example, osteoporosis and osteoarthritis, for what pertains to bone) and of the wide availability of synthetic mimics or inhibitors [ 120 , 121 ]. Also, in this case, scaffold-based delivery systems, in which these small compounds are encapsulated or immobilized through different procedures, may result in sustained local concentration of the active molecule [ 122 , 123 , 124 ].…”

Section: Msc-seeded Scaffolds As a Source Of Soluble Factorsmentioning

confidence: 99%

3D Bone Biomimetic Scaffolds for Basic and Translational Studies with Mesenchymal Stem Cells

Sobacchi

Erreni

Strina

et al. 2018

IJMS

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Mesenchymal stem cells (MSCs) are recognized as an attractive tool owing to their self-renewal and differentiation capacity, and their ability to secrete bioactive molecules and to regulate the behavior of neighboring cells within different tissues. Accumulating evidence demonstrates that cells prefer three-dimensional (3D) to 2D culture conditions, at least because the former are closer to their natural environment. Thus, for in vitro studies and in vivo utilization, great effort is being dedicated to the optimization of MSC 3D culture systems in view of achieving the intended performance. This implies understanding cell–biomaterial interactions and manipulating the physicochemical characteristics of biomimetic scaffolds to elicit a specific cell behavior. In the bone field, biomimetic scaffolds can be used as 3D structures, where MSCs can be seeded, expanded, and then implanted in vivo for bone repair or bioactive molecules release. Actually, the union of MSCs and biomaterial has been greatly improving the field of tissue regeneration. Here, we will provide some examples of recent advances in basic as well as translational research about MSC-seeded scaffold systems. Overall, the proliferation of tools for a range of applications witnesses a fruitful collaboration among different branches of the scientific community.

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“…miRNA is a type of endogenous small non‐coding RNA that often functioned through post‐transcriptional repression . Several miRNAs have been implicated in bone metabolism and osteogenic regulation . Our previous study has confirmed miR‐375 as a positive regulator in the osteogenic differentiation of MSCs, and overexpression of miR‐375 significantly enhanced the alkaline phosphatase (ALP) activity and calcium deposition in hASCs, suggesting that miR‐375‐mediated therapy might be a viable approach to repair bone defects .…”

Section: Introductionmentioning

confidence: 98%

Exosomes derived from miR‐375‐overexpressing human adipose mesenchymal stem cells promote bone regeneration

et al. 2019

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Objectives:The present study aimed to investigate whether exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells (hASCs) could enhance bone regeneration. Materials and Methods:Exosomes enriched with miR-375 (Exo [miR-375]) were generated from hASCs stably overexpressing miR-375 after lentiviral transfection and identified with transmission electron microscopy, nanosight and western blotting.The construction efficiency of Exo (miR-375) was evaluated with qRT-PCR and incubated with human bone marrow mesenchymal stem cells (hBMSCs) to optimize the effective dosage. Then, the osteogenic capability of Exo (miR-375) was investigated with ALP and ARS assays. Furthermore, dual-luciferase reporter assay and western blotting were conducted to reveal the underlying mechanism of miR-375 in osteogenic regulation. Finally, Exo (miR-375) were embedded with hydrogel and applied to a rat model of calvarial defect, and μ-CT analysis and histological examination were conducted to evaluate the therapeutic effects of Exo (miR-375) in bone regeneration. Results: miR-375 could be enriched in exosomes by overexpressing in the parent cells. Administration of Exo (miR-375) at 50 μg/mL improved the osteogenic differentiation of hBMSCs. With miR-375 absorbed by hBMSCs, insulin-like growth factor binding protein 3 (IGFBP3) was inhibited by binding to its 3′UTR, and recombinant IGFBP3 protein reduced the osteogenic effects triggered by Exo (miR-375). After incorporated with hydrogel, Exo (miR-375) displayed a slow and controlled release, and further in vivo analysis demonstrated that Exo (miR-375) enhanced the bone regenerative capacity in a rat model of calvarial defect. Conclusions: Taken together, our study demonstrated that exosomes derived from miR-375-overexpressing hASCs promoted bone regeneration. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Chen S, Tang Y, Liu Y, et al. Exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells promote bone regeneration. Cell

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The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

Cited by 79 publications

References 72 publications

Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration

Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration

3D Bone Biomimetic Scaffolds for Basic and Translational Studies with Mesenchymal Stem Cells

Exosomes derived from miR‐375‐overexpressing human adipose mesenchymal stem cells promote bone regeneration

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