Basic Research| Volume 44, ISSUE 9, P1396-1401, September 2018

C5L2 Silencing in Human Pulp Fibroblasts Enhances Nerve Outgrowth Under Lipoteichoic Acid Stimulation


      • Our results show that the previously less explored complement C5a receptor C5L2 constitutes a negative regulator of the neurite outgrowth under lipoteichoic acid stimulation.
      • Of the events occurring during dentin-pulp regeneration, nerve regeneration is the key factor for maintaining tooth viability after infection or injury.
      • A new mechanism of the complement system and the novel receptor identified in this study may provide a useful future therapeutic tool in targeting the pulp fibroblasts in the dentin-pulp regeneration process.



      We recently reported that caries-associated C5a receptor (C5aR) expression and activation result in up-regulation of brain-derived neurotropic factor secretion by pulp fibroblasts inducing prominent neurite outgrowth toward the carious site. Our data further showed a negative regulation of this brain-derived neurotropic factor secretion by C5L2, another C5aR. C5L2 was considered a nonfunctional receptor and thus has received much less attention than C5aR. The aim of this study was to identify the role of C5L2 in pulp fibroblast–mediated neurite outgrowth.


      In this study, lipoteichoic acid (LTA) was used to mimic dental caries–like inflammation. To evaluate the role of C5L2 in pulp neurite outgrowth, human pulp fibroblasts were C5L2 small interfering RNA silenced and cocultured with human neurons in a nerve growth assay system.


      C5L2 silencing drastically increased the neurite outgrowth toward the LTA-stimulated pulp fibroblasts. The number of neurites detected was increased in the LTA-treated pulp fibroblasts.


      Our results show that C5L2 constitutes a negative regulator of the neurite outgrowth under LTA stimulation. Of the events occurring during dentin-pulp regeneration, nerve regeneration is the key factor for maintaining tooth viability after infection or injury. Our study provides a foundation for creating therapeutic tools that target pulp fibroblasts during pulp/nerve regeneration.

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