Title: 1428 - The Complement Receptor C5L2 Negatively Regulates Odontoblastic Differentiation
Fanny chmilewsky (Presenter)
University of Illinois at Chicago
Ruiwei Liang, University of Illinois at Chicago
Anne George, University of Illinois at Chicago
Lyndon Cooper, University of Illinois at Chicago
Objectives: The dentin-pulp regeneration occurring under deep carious injury is a complex process resulting in the differentiation of dental pulp stem cells (DPSCs) in a new generation of functional odontoblast-like cells. Although the complement system, an important mediator of inflammation and tissue regeneration, is activated in the caries process, to date no investigation has explored the role of the complement receptor C5a receptor-like2 (C5L2) in dentin regeneration and stem cell biology. The aim of this study is to determine whether the complement receptor C5L2 participates in the differentiation of DPSCs into functional odontoblasts.
Methods: hDPSCs were cultured in regular or dentinogenic medium and incubated with or without tumor necrosis factor (TNF-α) and with or without SB203580, a p38MAPK inhibitor. The C5L2 expression was evaluated in hDPSCs by immunostaining and real-time PCR. The expression of DMP1 and DSPP was determined by real-time PCR on hDPSCs transfected with control or C5L2 siRNA. Finally, the expression of C5L2 in dental pulp was evaluated by immunohistochemistry in the sections of wild-type and DMP1-overexpressing mice.
Results: The results demonstrate that hDPSC express C5L2. This expression is subsequently increased during odontogenic differentiation and potentiated by TNFα. Interestingly, while p38MAPK controls the inflammation-mediated elevations in C5L2 expression by hDPSCs undergoing odontoblastic differentiation, it does not affect the basal level of C5L2 in hDPSCs undergoing odontoblastic differentiation. Importantly, the C5L2 silencing significantly increased DMP1 and DSPP expression in differentiated hDPSCs. Finally, we show for the first time that C5L2 is expressed in the pulp of mouse teeth and that this expression is higher in the sections of mice overexpressing DMP1.
Conclusions: This study demonstrates that the expression of C5L2 during odontoblastic differentiation is a complex process orchestrated by multiple signaling pathways and could play a critical role in regulating the differentiation of hDPSC’s and in dentin regeneration.
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE