Differential Expression Profiling of microRNAs in Human Placenta-Derived Mesenchymal Stem Cells Cocultured with Grooved Porous Hydroxyapatite Scaffolds

Deng, Li; Qing, Wei; Lai, Shuang; Zheng, Jiajun; Liu, Cong; Huang, Hao; Peng, Pairan; Mu, Yandong

doi:10.1089/dna.2021.0850

Cited by 5 publications

(9 citation statements)

References 61 publications

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“…[26][27][28] Consistently, we recently found that miRNA was differentially expressed during the induction of hPMSCs by HAG scaffolds. 20 Hydroxyapatite is a calcium phosphate bioceramic widely used in bone tissue repair and is widely accepted to be osteoinductive. 2,3 However, the microchannel structure may render the HAG scaffold more favorable for osteogenesis by increasing the surface area for cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous study, miR-129-5p was also found to be highly expressed in hPMSCs cocultured with HAG. 20 MiR-129-5p is a highly conserved miRNA in different species, including mice, rats, and humans (Figure 2C). Then, the relative expression of miR-129-5p under the above conditions was verified by real-time PCR (Figure 2D).…”

Section: Mir-129-5p Was Highly Expressed During Hag-induced Osteogeni...mentioning

confidence: 99%

“…Dysregulation of miRNAs is associated with bone degeneration. Recently, we revealed that miRNAs are differentially expressed during the osteogenic differentiation of human placenta‐derived mesenchymal stem cells (hPMSCs) induced by HAG scaffolds 20 . However, the role of miRNAs in this process has not been explored.…”

Section: Introductionmentioning

confidence: 99%

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A grooved porous hydroxyapatite scaffold induces osteogenic differentiation via regulation of PKA activity by upregulating miR‐129‐5p expression

Deng

Li²,

Ren

et al. 2022

J of Periodontal Research

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Background and objective Hydroxyapatite scaffolds with different morphologies have been widely used in bone tissue engineering. Moreover, microRNAs (miRNAs) have been proven to be extensively involved in regulating bone regeneration. We developed grooved porous hydroxyapatite (HAG) scaffolds with good osteogenic efficiency. However, little is known about the role of miRNAs in HAG scaffold‐mediated promotion of bone regeneration. The objective of this study was to reveal the mechanism from the perspective of differential miRNA expression. Methods Scanning electron microscopy (SEM) was used to perform the coculture of cells and scaffolds. The miRNA profiles were generated by a microarray assay. A synthetic miR‐129‐5p mimic and inhibitor were used for overexpression or inhibition. The expression of osteogenic marker mRNAs and proteins was detected by quantitative real‐time PCR (qRT–PCR), Western blotting, and immunofluorescence. An ALP activity kit and alizarin red staining (ARS) were used to measure ALP activity and mineral deposition formation. Cell migration ability was examined by wound healing and transwell assays. Protein kinase A (PKA) activity was measured by enzyme‐linked immunosorbent assay (ELISA) after miR‐129‐5p transfection. Target genes were identified by a dual‐luciferase reporter assay. H89 preculture evaluated the cross talk between miR‐129‐5p and PKA activity. Heterotopic implantation models, hematoxylin–eosin (HE), immunohistochemistry staining, and micro‐CT were used to evaluate miR‐129‐5p osteogenesis in vivo. Results miRNAs were differentially expressed during osteogenic differentiation induced by HAG in vitro and in vivo. miR‐129‐5p was the only highly expressed miRNA both in vitro and in vivo. miR‐129‐5p overexpression promoted osteoblast differentiation and cell migration, while its inhibition weakened the effect of HAG. Moreover, miR‐129‐5p activated PKA to regulate the phosphorylation of β‐catenin and cAMP‐response element binding protein (CREB) by inhibiting cAMP‐dependent protein kinase inhibitor alpha (Pkia). H89 prevented the effects of miR‐129‐5p on osteogenic differentiation and cell migration. HE, immunohistochemistry staining and micro‐CT results showed that miR‐129‐5p promoted in vivo osteogenesis of the HAG scaffold. Conclusion The HAG scaffold activates Pka by upregulating miR‐129‐5p and inhibiting Pkia, resulting in CREB‐dependent transcriptional activation and accumulation of β‐catenin and promoting osteogenic marker expression.

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Section: Discussionmentioning

confidence: 99%

Section: Mir-129-5p Was Highly Expressed During Hag-induced Osteogeni...mentioning

confidence: 99%

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A grooved porous hydroxyapatite scaffold induces osteogenic differentiation via regulation of PKA activity by upregulating miR‐129‐5p expression

Deng

Li²,

Ren

et al. 2022

J of Periodontal Research

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“…Our previous study revealed that miR-210-3p was upregulated in HAG scaffold induced osteogenic differentiation [16]. miR-210-3p is a highly conserved miRNA from mouse to humans (sequence: CUG UGC GUG UGA CAG CGG CUGA).…”

Section: Mir-210-3p Inhibited the Osteogenic Differentiation Of Mc3t3...mentioning

confidence: 99%

“…They found that the activity of miRNA in hMSCs was closely related to the nanotopographical cues and that the nanotopographical cues regulated the osteogenic differentiation of hMSCs via modulating lncRNAs [ 15 ]. Recently, we found that miRNAs were differentially expressed during osteogenesis induced by HAG scaffolds, and miR-210-3p was one of the significantly up-regulated miRNAs [ 16 ]. However, its role of osteogenic differentiation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

miR-210-3p suppresses osteogenic differentiation of MC3T3-E1 by targeting brain derived neurotrophic factor (BDNF)

et al. 2022

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Background and objective As an important mediator of intercellular interaction and formation of extracellular bone matrix, porous scaffolds are widely used for bone regeneration. Accumulating evidences demonstrate that microRNA are involved in the regulation of scaffolds-induced bone regeneration. Recently, we revealed that miR-210-3p was highly expressed during osteogenesis induced by HAG. In present study, we further explored the molecular mechanism underlying the effect of miR-210-3p on osteogenic differentiation. Materials and methods In this study, miR-210-3p mimics and inhibitors were synthesized and transfected into MC3T3-E1 cells to explore their effects on osteogenic differentiation. The expression of osteogenic marker (Alp and Runx2) were detected by real-time quantitative PCR (qRT-PCR) and western blotting. After osteogenesis induction for 7 days, Alp staining were used to detected osteoblast differentiation of MC3T3-E1 cells. CCK8 and Transwell assays were performed to detected cell proliferation and migration. Then, top ranking list of target genes of miR-210-3p obtained from TargetScan and the expression of BDNF were detected by qRT-PCR and ELISA. The relationship between miR-210-3p and BDNF was verified by luciferase report assay. Furthermore, the effect of BDNF on osteoblast differentiation was verified by transfecting siRNA or adding BDNF to the culture medium. Results MiR-210-3p mimics markedly suppress osteogenic differentiation, cell migration and cell proliferation of MC3T3-E; nevertheless, silencing of miR-210-3p dramatically enhanced MC3T3-E1 osteogenesis, cell migration and proliferation. Furthermore, luciferase reporter assay verified that brain derived neurotrophic factor (BDNF) is a directly target of miR-210-3p. Moreover, BDNF siRNA significantly decreased the expression levels of ALP and cell migration. The addition of BDNF partially rescued the inhibition of osteogenesis by miR-210-3p. Conclusion miR-210-3p inhibited the osteogenic differentiation via targeting BDNF. Our Results provide a promising target for regulating osteogenic differentiation.

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Bone marrow mesenchymal stem cell-derived exosomes loaded with miR-26a through the novel immunomodulatory peptide DP7-C can promote osteogenesis

Lai,

Deng,

Liu

et al. 2023

Biotechnol Lett

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Purpose: As small bioactive molecules, exosomes can deliver osteogenesis-related miRNAs to target cells and promote osteogenesis. This study aimed to investigate miR-26a as a therapeutic cargo to be loaded into exosomes through a novel immunomodulatory peptide (DP7-C). In addition, the exosomes secreted from BMSCs were obtained to evaluate their osteogenic capacity.Methods: After transfecting BMSCs with DP7-C as a transfection agent, exosomes were extracted by ultracentrifugation from the culture supernatant of miR-26a-modi ed BMSCs. Then, we characterized and identi ed the engineered exosomes. Next, the effect of the engineered exosomes on osteogenesis was evaluated in vitro and in vivo, including in Transwell, wound healing, modi ed Alizarin red staining, western blot, real-time quantitative PCR, and experimental periodontitis assays. Finally, bioinformatics and data analysis were used to investigate the role of miR-26a in bone regeneration.Results: The DP7-C/miR-26a complex successfully transfected miR-26a into BMSCs and stimulated them to release a high dosage of exosomes overexpressing miR-26a. Furthermore, exosomes loaded with miR-26a could promote the proliferation, migration, and osteogenic differentiation of BMSCs in vitro and inhibit the destruction of periodontitis in vivo, maintaining the integrity of supporting periodontal tissue. Target gene analysis indicated that the osteogenic effect of miR-26a is related to the mTOR pathway.Conclusion: MiR-26a can be encapsulated into exosomes through DP7-C. Exosomes loaded with miR-26a can promote osteogenesis and inhibit bone loss in experimental periodontitis and serve as the foundation for a novel treatment strategy.

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Differential Expression Profiling of microRNAs in Human Placenta-Derived Mesenchymal Stem Cells Cocultured with Grooved Porous Hydroxyapatite Scaffolds

Cited by 5 publications

References 61 publications

A grooved porous hydroxyapatite scaffold induces osteogenic differentiation via regulation of PKA activity by upregulating miR‐129‐5p expression

A grooved porous hydroxyapatite scaffold induces osteogenic differentiation via regulation of PKA activity by upregulating miR‐129‐5p expression

miR-210-3p suppresses osteogenic differentiation of MC3T3-E1 by targeting brain derived neurotrophic factor (BDNF)

Bone marrow mesenchymal stem cell-derived exosomes loaded with miR-26a through the novel immunomodulatory peptide DP7-C can promote osteogenesis

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