Abstract
The developmental dysfunction of cartilage progenitor cells (CPCs) causes dwarfism. Radical therapies for dwarfism remain underdeveloped. Recently, the therapeutic benefits of extracellular vesicles (EVs) released from human exfoliated deciduous tooth-derived stem cells (SHED) have been investigated for their potential to restore disease-target cells. However, the effects of EVs on human CPCs for the treatment of dwarfism remain unclear. We investigated the impact of EVs on cell proliferation, telomerase activity, telomerase reverse transcriptase (TERT) expression, cell cycle, and extracellular signal-regulated protein kinase 1/2 (ERK1/2) levels in human CPCs and in our established osteogenesis imperfecta (OI)-specific SHED (OI-SHED). EVs enhanced the proliferation and G1/S phase transition of CPCs, which was associated with increased TERT expression and telomerase activity. However, RNase-preconditioned EVs did not attenuate the efficacy of EVs in CPCs. ERK1/2 inhibitor tests demonstrated that CPCs exhibited suppressed proliferation, telomerase activity, and G1/S phase progression. EV-transferring CD29 induced ERK1/2 phosphorylation in CPCs, subsequently activating telomerase activity to induce proliferation. Interestingly, EV stimulation restored the reduction in cell proliferation, cell cycle progression, phosphorylated ERK1/2 levels, and TERT expression in OI-SHED. In conclusion, the present findings provide new insights into ERK1/2-mediated proliferation of human CPCs using EVs.
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Acknowledgements
We thank the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences, for the technical assistance with cell sorting using FACSAria Fusion cell sorter and FACDiva software (BD Biosciences). This was partially supported by the Mitsuaki Shiraishi Fund for Basic Medical Research. Finally, we thank Editage (https://www.editage.jp) for the English editing of our manuscript.
Funding
This work was supported by JSPS KAKENHI grants JP22K19565 (T.Y.), JP23H03071 (T.Y.), JP23K27762 (T.Y.), JP21K16932 (S.S.), JP24K12873 (S.S.), and JP21J10881 (S.M.).
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SM and SS: study design, collection, analysis and interpretation of data, and statistical analysis. Y.K-N., M.M.S., L.Y., R.A., E.Y–T., M.F.Z., H.K., N.U., and H.Y.: assembly of data and statistical analysis. T.Y.: study conception and design, manuscript drafting, and critical revision of the manuscript for important intellectual content. All the authors approved the final version of the manuscript.
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Murata, S., Sonoda, S., Kyumoto-Nakamura, Y. et al. Deciduous pulp stem cell-derived extracellular vesicles stimulate the proliferation of cartilage progenitor cells via extracellular signal-regulated protein kinase 1/2 activation. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37380-7
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DOI: https://doi.org/10.1038/s41598-026-37380-7
