Evidence map›Paper›PMID 39956898›Full record

ArticleJournal of translational medicine2025

MicroRNA-27a transfected dental pulp stem cells undergo odonto/osteogenic differentiation via targeting DKK3 and SOSTDC1 in Wnt/BMP signaling in vitro and enhance bone formation in vivo.

Ziniu Yu, Nobuyuki Kawashima, Keisuke Sunada-Nara, Shihan Wang, Peifeng Han, Thoai Quoc Kieu, Chunmei Ren, Sonoko Noda, Kento Tazawa, Takashi Okiji

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Ziniu YuDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0009-0005-0533-5664
Nobuyuki KawashimaDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan. kawashima.n.endo@tmd.ac.jp.ORCID 0000-0002-1636-0487
Keisuke Sunada-NaraDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0000-0002-1023-1529
Shihan WangDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0009-0000-9926-9533
Peifeng HanDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0000-0002-1442-9102
Thoai Quoc KieuDepartment of Pediatric Dentistry, Faculty of Odonto-Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, 17000, Vietnam.
Chunmei RenDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0009-0004-8565-3728
Sonoko NodaDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0000-0001-9981-8344
Kento TazawaDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0000-0001-9725-6034
Takashi OkijiDepartment of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Formerly Tokyo Medical and Dental University, Tokyo, 113-8549, Japan.ORCID 0000-0002-9791-4508

Funding

Japan Science and Technology Agency 51BA216002Japan Science and Technology Agency 51BA216012Japan Science and Technology Agency 51BA216023Japan Society for the Promotion of Science 22K09960ZAJapan Society for the Promotion of Science 23K15994ZAJapan Society for the Promotion of Science 24K12909ZAJapan Society for the Promotion of Science 24K19891ZA
6 · The paper itself

Abstract

backgroundMicroRNAs (miRNAs) play a crucial role in cell differentiation through epigenetic regulation of gene expression. In human dental pulp cells, we have identified miRNA-27a being upregulated under inflammatory conditions. Here, we aimed to examine whether (i) overexpression of miRNA-27a in human dental pulp stem cells (hDPSCs) enhances their odonto/osteoblastic differentiation via Wnt and bone morphogenetic protein signaling; and (ii) hDPSCs overexpressing miRNA-27a promote new bone formation in vivo.

methodshDPSCs were cultured in osteogenic medium to promote differentiation. To examine the role of miRNA-27a, hDPSCs were transfected with either a miRNA-27a mimic to enhance or an inhibitor to suppress miRNA-27a expression. Odonto/osteoblastic differentiation was assessed by evaluating the expression of specific markers, Wnt and bone morphogenetic protein (BMP) signaling molecules, and mineralization capacity using RT-qPCR, western blotting, Alizarin Red S (ARS) staining, and alkaline phosphatase (ALP) activity. Potential miRNA-27a binding sites in the 3'UTRs of DKK3 and SOSTDC1 were identified via bioinformatics analysis and validated through the luciferase reporter assay. In vivo, miRNA-27a-overexpressing hDPSCs were seeded into collagen honeycomb scaffolds and implanted into mouse calvarial bone cavities to assess new bone formation.

resultsMiRNA-27a was highly upregulated in hDPSCs committed to odonto/osteoblastic differentiation. Overexpression of miRNA-27a led to increased expression of odonto/osteoblastic markers and enhanced mineralization capacity, while inhibition of miRNA-27a had the opposite effect. MiRNA-27a targeted DKK3, promoting β-catenin nuclear translocation and inhibiting SOSTDC1, which enhanced SMAD1/5 phosphorylation. Binding sites for miRNA-27a were identified in the 3'UTRs of DKK3 and SOSTDC1. In vivo, miRNA-27a-overexpressing hDPSCs promoted new bone formation in mouse calvaria bone cavities.

conclusionTransfection of miRNA-27a in hDPSCs enhanced their odonto/osteoblastic differentiation by targeting DKK3 and SOSTDC1, thereby promoting the Wnt and BMP signaling. Transplantation of miRNA-27a-overexpressing hDPSCs promoted new bone formation in vivo. These findings deepen our understanding of the effects of miRNA on Wnt and BMP pathways and suggest a potential clinical application for miRNA-27a in promoting hard tissue regeneration, offering a promising therapeutic target for dental and craniofacial tissue reconstruction.

Indexed as

Bone Morphogenetic ProteinsCell DifferentiationDental PulpIntercellular Signaling Peptides and ProteinsMicroRNAsOsteogenesisStem CellsTransfectionWnt Signaling Pathway3' Untranslated RegionsAdaptor Proteins, Signal TransducingAnimalsBase SequenceChemokinesFrizzled-Related ProteinsHumans3' Untranslated RegionsAdaptor Proteins, Signal TransducingBone Morphogenetic ProteinsChemokinesDKK3 protein, humanFrizzled-Related ProteinsIntercellular Signaling Peptides and ProteinsIntracellular Signaling Peptides and ProteinsMicroRNAsMIRN27 microRNA, humanBinding sitesCell differentiationDental pulp stem cellsmicroRNA-27aSignal transductionTissue engineering

Identifiers

PMID39956898
PMCPMC11831854

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.