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J Oral Rehabil. 2019 Jul 10. doi: 10.1111/joor.12859. [Epub ahead of print]

IGF2 enhanced the osteo-/dentinogenic and neurogenic differentiation potentials of stem cells from apical papilla.

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Laboratory of Molecular Signaling and Stem Cells Therapy, Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, Beijing, 100050, China.
Department of Pediatric dentistry, Capital Medical University School of Stomatology, Beijing, 100050, China.



In dental tissue engineering, niche is important for maintaining stem cells function and regenerating the dental tissues. However, there is limited knowledge for the growth factors in niche to maintain the function of stem cells. In this study, we investigated the effect of IGF2, a growth factor in stem cells from apical papilla (SCAPs) niche, on differentiation and proliferation potentials of SCAPs.


Recombinant human IGF2 protein (rhIGF2) was used. CCK-8 assay, CFSE assay, alkaline phosphatase (ALP) activity, Alizarin Red staining, quantitative calcium analysis, immunofluorescence staining and Real-time RT-PCR were performed to investigation the cell proliferation and differentiation potentials of SCAPs. And proteomic analysis was used to identify the differential secreted proteins.


By ALP activity assay, we found that 5 ng/ml rhIGF2 might be the optimal concentration for treatment. Then Alizarin Red staining, quantitative calcium analysis, and osteogenesis related gene expression results showed that 5 ng/ml rhIGF2 could enhance the osteo-/dentinogenic differentiation potentials in SCAPs. Immunofluorescence staining and Real-time RT-PCR results showed that neurogenic markers were significantly induced by 5 ng/ml rhIGF2 in SCAPs. Then, CCK-8 assay and CFSE assay results showed that 5 ng/ml rhIGF2 could enhance the cell proliferation in SCAPs. Furthermore, proteomic analysis showed that IGF2 could induce some secreted proteins which function related to the osteogenesis, neurogensis and cell proliferation.


Our results identified that IGF2 might be the potential mediator in niche to promote SCAPs function and dental tissue regeneration. This article is protected by copyright. All rights reserved.


IGF2; Neurogenic differentiation; Niche; Osteo-/dentinogenic differentiation; Proliferation; Stem cells from apical papilla


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