Abstract

We examined the effects of bone morphogenetic protein-2 (BMP-2) on growth, differentiation, and intracellular signaling pathways of odontoblast-like cells, KN-3 cells, to clarify molecular mechanisms of odontoblast differentiation during pulp regeneration process. After treatment with BMP-2, the cell morphology, growth, alkaline phosphatase (ALP) activity, and the activation and expression of BMP-induced intracellular signaling molecules, such as Smad1/5/8 and Smad6/7, as well as activities of dentin sialoprotein (DSP) and dentin matrix protein 1 (DMP1), were examined. BMP-2 had no effects on the morphology, growth, or ALP activity of KN-3 cells, whereas it induced the phosphorylation of Smad1/5/8 and expression of Smad6/7. BMP-2 also induced the expressions of DSP and DMP-1. Our results suggest that KN-3 cells may express an odontoblastic phenotype with the addition of BMP-2 through the activation of Smad signaling pathways.

Highlights

  • When dental pulp is exposed to external stimuli such as bacterial infection and following restorative procedures, a wound healing process is induced, and surviving odontoblasts and odontoblast-like cells differentiated from progenitor or stem cells form reactionary and reparative dentin to block further external stimuli [1,2,3]

  • To understand molecular mechanisms of the differentiation of KN-3 cells into functional odontoblast-like cells, we examined the effects of bone morphogenetic protein-2 (BMP-2) on the cell growth, differentiation, and the involvement of Smads signaling pathways in the responses of KN-3 cells on BMP-2

  • The alkaline phosphatase (ALP) activity of KN-3 cells after confluence increased in a time-dependent manner, regardless of exposure to BMP-2 (Figure 1(c))

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Summary

Introduction

When dental pulp is exposed to external stimuli such as bacterial infection and following restorative procedures, a wound healing process is induced, and surviving odontoblasts and odontoblast-like cells differentiated from progenitor or stem cells form reactionary and reparative dentin to block further external stimuli [1,2,3]. Several studies have focused on clarification of a common mechanism existing in wound healing and regeneration of dental pulp in order to overcome the limitations of present methods to preserve vital dental pulp and develop effective pulp regeneration therapies; the molecular mechanisms of odontoblastic cells activated by BMP-2 are not fully understood. The regulation mechanisms of Runx2/Smad and other cascades controlled by BMP-2 during osteoblast and odontoblast differentiation from mesenchymal stem cells have been extensively studied [12,13,14,15,16,17]. The combination of BMP-2 with a collagen sponge was recently approved by the US Food and Drug Administration for clinical use such as oral maxillofacial surgery [18], International Journal of Dentistry while further studies have focused on development of an effective method based on available clinical data as well as to understanding the effects of BMP-2

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