Evidence map›Paper›PMID 33759282›Full record

ArticleCell proliferation2021

Periodontitis-compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA-378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling.

Huan Zhou, Xuan Li, Rui-Xin Wu, Xiao-Tao He, Ying An, Xin-Yue Xu, Hai-Hua Sun, Li-An Wu, Fa-Ming Chen

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In one paragraph

Article in Cell proliferation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed.

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  9. Isolation methods of exosomes derived from dental stem cells.International journal of oral science · 2025
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  14. Article
  15. Angiogenic regulation of dental pulp stem cells.Frontiers in dental medicine · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Huan ZhouDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Xuan LiDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Rui-Xin WuDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Xiao-Tao HeDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Ying AnDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Xin-Yue XuDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Hai-Hua SunDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Li-An WuDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.
Fa-Ming ChenDepartment of Periodontology, School of Stomatology, State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Fourth Military Medical University, Xi'an, China.ORCID https://orcid.org/0000-0002-8398-2104

Funding

Changjiang Scholars Program of the Ministry of Education of the People's Republic of China (2016)National Natural Science Foundation of China 81700971National Natural Science Foundation of China 81771095National Natural Science Foundation of China 81970947Shaanxi Key Scientific and Technological Innovation Team 2017KCT-32
6 · The paper itself

Abstract

objectivesPreviously, our investigations demonstrated robust pro-angiogenic potentials of extracellular vesicles secreted by periodontitis-compromised dental pulp stem cells (P-EVs) when compared to those from healthy DPSCs (H-EVs), but the underlying mechanism remains unknown. MATERIALS AND

methodsHere, circulating microRNAs (miRNAs) specifically found in P-EVs (compared with H-EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P-EV-enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay. CCK-8, transwell/scratch wound healing and tube formation assays were established to investigate the proliferation, migration, and tube formation abilities of endothelial cells (ECs). Western blot was employed to measure the protein levels of Hedgehog/Gli1 signalling pathway components and angiogenesis-related factors.

resultsThe angiogenesis-related miRNA miR-378a was found to be enriched in P-EVs, and its role in P-EV-enhanced cell angiogenesis was confirmed, wherein Sufu was identified as a downstream target gene of miR-378a. Functionally, silencing of Sufu stimulated EC proliferation, migration and tube formation by activating Hedgehog/Gli1 signalling. Further, we found that incubation with P-EVs enabled the transmission of P-EV-contained miR-378a to ECs. Subsequently, the expressions of Sufu, Gli1 and vascular endothelial growth factor in ECs were significantly influenced by P-EV-mediated miR-378a transmission.

conclusionsThese data suggest that P-EVs carrying miR-378a promote EC angiogenesis by downregulating Sufu to activate the Hedgehog/Gli1 signalling pathway. Our findings reveal a crucial role for EV-derived miR-378a in cell angiogenesis and hence offer a new target for modifying stem cells and their secreted EVs to enhance vessel regenerative potential.

Indexed as

Neovascularization, PhysiologicSignal TransductionAntagomirsCell MovementCell ProliferationDental PulpExtracellular VesiclesHedgehog ProteinsHumansHuman Umbilical Vein Endothelial CellsMicroRNAsPeriodontitisPyridinesPyrimidinesRepressor ProteinsRNA InterferenceAntagomirsGANT 61GLI1 protein, humanHedgehog ProteinsMicroRNAsMIRN3978 microRNA, humanPyridinesPyrimidinesRepressor ProteinsRNA, Small InterferingSUFU protein, humanZinc Finger Protein GLI1angiogenesisdental pulp stem cellsextracellular vesiclesperiodontitisSufu

Identifiers

PMID33759282
PMCPMC8088471

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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.