Deciduous pulp stem cell-derived extracellular vesicles stimulate the proliferation of cartilage progenitor cells via extracellular signal-regulated protein kinase 1/2 activation

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.