Evidence map›Paper›PMID 41225501›Full record

ArticleStem cell research & therapy2025

Investigations into the basal neural-like properties of dental pulp stem cells reveal they possess a functional type 2 muscarinic receptor which regulates quiescence.

S Alqahtani, A Gibbs, M Verma, O Baradwan, K Jubiar, M A Alonazi, W McLean, C J Nile

Abstract read
In one paragraph

Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
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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

8 authors.

S AlqahtaniDepartment of Restorative Dental Sciences, College of Dentistry, Jouf University, Al-Jouf, Saudi Arabia.
A GibbsSchool of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK.
M VermaSchool of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK.
O BaradwanDepartment of Restorative Dental Sciences, College of Dentistry, Jouf University, Al-Jouf, Saudi Arabia.
K JubiarOral Sciences Research Group, University of Glasgow, 378 Sauchiehall Street, Glasgow, G2 3JZ, UK.
M A AlonaziDepartment of Restorative Dental Sciences, College of Dentistry, Jouf University, Al-Jouf, Saudi Arabia.
W McLean *Oral Sciences Research Group, University of Glasgow, 378 Sauchiehall Street, Glasgow, G2 3JZ, UK.
C J Nile *School of Dental Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4BW, UK. christopher.nile1@newcastle.ac.uk.ORCID http://orcid.org/0000-0001-8218-2167

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDental pulp stem cells (DPSCs) are a population of mesenchyme-derived cells residing within the dental pulp known for their multipotent differentiation potential and neural-like properties. While a functional cholinergic system has been described in various mesenchymal stem cell (MSC) populations, muscarinic receptor mediated cholinergic signalling remains unexplored in DPSCs.

methodsThe expression of neurotransmitter-associated genes was investigated using a targeted array panel and immunocytochemistry. Functionality of acetylcholine receptors (AChRs) was confirmed using receptor-specific agonists and antagonists. The effects of type 2 muscarinic receptor (m2AChR) signalling on DPSCs viability and proliferation were evaluated using an LDH release assay, CCK-8 assay and annexin V/PI staining. The effect of m2AChR signalling on the cell cycle was determined by flow cytometry and gene expression profiling, and the downstream effects on DPSCs osteogenic differentiation and migration were determined using an osteogenic differentiation assay and a wound healing assay. Finally, the effect of m2AChR signalling on the transcriptome was determined by RNAseq and the role of the MAPK/ERK pathway in mediating m2AChR signalling determined using an in-cell ELISA.

resultsAnalysis of the neurotransmitter profile of DPSCs revealed they have cholinoceptive properties and pharmacological investigations confirmed they express a functional m2AChR. Activation of the m2AChR led to a reversible reduction in DPSCs proliferation, without compromising cell viability or pluripotency. Flow cytometric analysis and gene expression profiling confirmed that activation of the m2AChR caused cell cycle arrest at the G2/M phase which coincided with upregulated expression of CDKN1A (P21), a canonical marker of quiescence. Activation of the DPSC m2AChR also impaired their migration and osteogenic differentiation capabilities. RNAseq analysis revealed differentially expressed genes involved in regulating the cell cycle and MAPK/ERK signalling. Furthermore, analysis of ERK1/2 phosphorylation suggested that the MAPK/ERK pathway may play a role in m2AChR mediated regulation of quiescence.

conclusionsDPSCs exhibit cholinoceptive properties, and activation of the m2AChR engages the MAPK/ERK pathway and is associated with a reversible cell-cycle arrest consistent with a quiescent-like state, without affecting viability or pluripotency. These data support the m2AChR as a putative target for manipulating DPSC behaviour and transient quiescence in future regenerative applications.

Indexed as

Dental PulpStem CellsCell CycleCell DifferentiationCell ProliferationCells, CulturedHumansMesenchymal Stem CellsOsteogenesisAcetylcholineCholinergic receptorsDental pulp stem cellsMuscarinic type 2 receptorNeurotransmitters

Identifiers

PMID41225501
PMCPMC12613501

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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.