Evidence map›Paper›PMID 42778936›Full record

ArticleCell communication and signaling : CCS2026

Targetome-defined miR-181c signaling from extracellular vesicles governs periodontal MSC fate via RNF150-MAP3K5.

Jingyi Gao, Anhao Liu, Ye Yint Kaung Myint, Masahiro Hatasa, Supreda Suphanantachat Srithanyarat, Takanori Iwata

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Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jingyi GaoDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Anhao LiuDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Ye Yint Kaung MyintDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Masahiro HatasaDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Supreda Suphanantachat SrithanyaratDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
Takanori IwataDepartment of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. iwata.peri@tmd.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn regenerative settings, robust differentiation of human mesenchymal stromal cells (hMSCs) requires precise coupling between post-transcriptional regulation and kinase-driven pathways to achieve optimal therapeutic efficacy. miRNA-mediated regulation is widely implicated in stem cell fate control, yet its mechanistic contribution to lineage commitment remains incompletely defined.

methodsMulti-conditioned periodontal ligament-derived hMSCs were developed as the regenerative model for alveolar bone. Extracellular vesicle (EV)-encapsulated miRNAs were delineated through microarrays. AGO2 RNA-immunoprecipitation sequencing with transcriptome profiling was integrated to establish the miRISC-associated targetome. Protein-protein interactions and signaling hierarchy were examined by Co-IP, WB, and IFC under knockdown/overexpression with pharmacological interventions. The translational efficacy of EV and miRNA was validated using a mouse ligature-induced periodontitis model, followed by µCT and histological analyses.

resultsEVs produced by hMSCs with higher intrinsic osteogenic capacity exhibited enhanced osteo-inductivity, traced to the enrichment of miR-181c. miR-181c was consistently upregulated during osteogenesis, with gain- and loss-of-function producing concordant effects. Mechanistically, the E3 ubiquitin ligase RNF150 emerged as the main target, whose repression reduced MAP3K5 ubiquitin-mediated proteolysis and enabled p38 activation. Local administration of EVs and miR-181c both promoted alveolar bone regeneration process in vivo.

conclusionCollectively, EV-miR-181c-RNF150-MAP3K5-p38 axis was proposed linking miRNA-mediated repression to kinase activation and lineage commitment. This work provides the framework for how EV-delivered miRNAs gate hMSCs' fate decision, with significance for acellular therapeutic modalities in periodontal and skeletal tissues.

Indexed as

Extracellular VesiclesMesenchymal Stem CellsMicroRNAsPeriodontal LigamentSignal TransductionUbiquitin-Protein LigasesAnimalsCell DifferentiationCell LineageHumansMiceMitogen-Activated Protein Kinase Kinase Kinase 11OsteogenesisMicroRNAsMIrn181 microRNA, humanMitogen-Activated Protein Kinase Kinase Kinase 11Ubiquitin-Protein LigasesDifferentiationExtracellular vesiclesHuman mesenchymal stromal cellsMicroRNAsOsteogenesis

Identifiers

PMID42778936
PMCPMC13599342

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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.