| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3147641 | Journal of Endodontics | 2016 | 7 Pages |
•hDPSCs express markers for glutamatergic, GABAergic, and dopaminergic neurons.•PIN1 overexpression induced glutamatergic and GABAergic differentiation of hDPSCs.•PIN-modulated hDPSCs may serve as useful sources in degenerative disorders of the CNS.•PIN modulated hDPSCs may attenuate the symptoms of neuropathic orofacial pain.
IntroductionThe purpose of this study was to investigate the role of protein interacting with never in mitosis A-1 (PIN1) in the neuronal or glial differentiation of human dental pulp stem cells (hDPSCs) and whether PIN1 can regulate determination of neuronal sub-phenotype.MethodsAfter magnetic-activated cell sorting to separate CD34+/c-kit+/STRO-1+ hDPSCs, cells were cultured in neurogenic medium. Differentiation was measured as Nissl staining and marker protein or mRNA expression by reverse transcriptase polymerase chain reaction, immunofluorescence, and flow cytometric analysis.ResultsPIN1 mRNA levels were upregulated in a time-dependent fashion during neurogenic differentiation. The PIN1 inhibitor juglone suppressed neuronal differentiation but promoted glial differentiation as assessed by the number of Nissl-positive cells and mRNA expression of neuronal markers (nestin, βIII-tubulin, and NeuN) and a glial marker (glial fibrillary acidic protein). Conversely, overexpression of PIN1 by infection with adenovirus-PIN1 increased neuronal differentiation but decreased glial differentiation. Moreover, PIN1 overexpression increased the percentage of glutamatergic and GABAergic cells but decreased that of dopaminergic cells among total NeuN-positive hDPSCs.ConclusionsThis is the first study to demonstrate that PIN1 overexpression induced glutamatergic and GABAergic neuronal differentiation but suppressed glial differentiation of hDPSCs, suggesting that enhancing PIN expression is important to obtain human glutamatergic and GABAergic neurons from hDPSCs.
