Epiregulin can promote proliferation of stem cells from the dental apical papilla via MEK/Erk and JNK signalling pathways
Article first published online: 5 JUL 2013
© 2013 John Wiley & Sons Ltd
Volume 46, Issue 4, pages 447–456, August 2013
How to Cite
Cao, Y., Xia, D. S., Qi, S. R., Du, J., Ma, P., Wang, S. L. and Fan, Z. P. (2013), Epiregulin can promote proliferation of stem cells from the dental apical papilla via MEK/Erk and JNK signalling pathways. Cell Proliferation, 46: 447–456. doi: 10.1111/cpr.12039
- Issue published online: 21 JUL 2013
- Article first published online: 5 JUL 2013
- Manuscript Accepted: 24 MAR 2013
- Manuscript Received: 16 FEB 2013
- National Natural Science Foundation of China. Grant Numbers: 81271101, 81141010, 30901692
- National Basic Research Program of China. Grant Number: 2010CB944801
- Science Facility in Institutions of Higher Learning Under the jurisdiction of Beijing Municipality. Grant Number: PXM2011_014226_07_000066
- Beijing Municipal Science and Technology Commission. Grant Number: Z121100005212004
- Beijing Natural Science Foundation. Grant Number: 7102067
Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but their molecular mechanisms of differentiation and proliferation remain unclear; this situation has restricted use of MSCs to a limited number of applications. A previous study of ours found a member of the epidermal growth factor family, epiregulin (EREG), to be involved in regulation of MSC differentiation. In the present study, we have used human dental stem cells from the apical papilla (SCAPs) to investigate the role of EREG on proliferation of MSCs.
Materials and methods
SCAPs were isolated from apical papillae of immature third molars. Retroviral short hairpin RNA (shRNA) was used to silence EREG gene expression, and human recombinant EREG protein was used to stimulate SCAPs. SCAP proliferation was examined using tetrazolium dye colorimetric assay/cell growth curve. Western blotting was performed to detect expressions of extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), mitogen-activated protein kinases 1 and 2 (MEK1/2), protein kinase B (Akt), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK).
Depletion of EREG with shRNA inhibited SCAP proliferation and repressed phosphorylation of Erk1/2 and JNK. Human recombinant EREG protein promoted cell proliferation and enhanced Erk1/2, MEK and JNK phosphorylation in SCAPs. Furthermore, blocking MEK/Erk signalling with specific Erk1/2 inhibitor PD98059, or JNK signalling with specific inhibitor SP600125, abolished effects of EREG on cell proliferation.
These findings indicate that EREG could enhance cell proliferation in dental tissue-derived MSCs by activating MEK/Erk and JNK signalling pathways.