Complement C5aR/LPS-induced BDNF and NGF modulation in human dental pulp stem cells

Stem cells with the ability to differentiate into a variety of cells and secrete nerve regeneration factors have become an emerging option in nerve regeneration. Dental pulp stem cells (DPSCs) appear to be a good candidate for nerve regeneration given their accessibility, neural crest origin, and ne...

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Published in:	Scientific reports 2022-02, Vol.12 (1), p.2042-2042, Article 2042
Main Authors:	Irfan, Muhammad, Kim, Ji Hyun, Druzinsky, Robert E, Ravindran, Sriram, Chung, Seung
Format:	Article
Language:	eng
Subjects:	Axonogenesis Bone marrow Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - metabolism Cell differentiation Complement component C5a Dental pulp Dental Pulp - cytology Enzyme-linked immunosorbent assay Fibroblasts Humans Inflammation Lipopolysaccharides Lipoteichoic acid Mesenchymal Stem Cells - metabolism Mesenchyme Nerve growth factor Nerve Growth Factor - metabolism Nerve Regeneration - genetics Neural crest Receptor, Anaphylatoxin C5a - physiology Regeneration Stem cells Stem Cells - metabolism Stem Cells - physiology
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Summary:	Stem cells with the ability to differentiate into a variety of cells and secrete nerve regeneration factors have become an emerging option in nerve regeneration. Dental pulp stem cells (DPSCs) appear to be a good candidate for nerve regeneration given their accessibility, neural crest origin, and neural repair qualities. We have recently demonstrated that the complement C5a system, which is an important mediator of inflammation and tissue regeneration, is activated by lipoteichoic acid-treated pulp fibroblasts, and governs the production of brain-derived nerve growth factor (BDNF). This BDNF secretion promotes neurite outgrowth towards the injury site. Here, we extend our observation to DPSCs and compare their neurogenic ability to bone marrow-derived mesenchymal stem cells (BM-MSCs) under inflammatory stimulation. Our ELISA and immunostaining data demonstrate that blocking the C5a receptor (C5aR) reduced BDNF production in DPSCs, while treatment with C5aR agonist increased the BDNF expression, which suggests that C5aR has a positive regulatory role in the BDNF modulation of DPSCs. Inflammation induced by lipopolysaccharide (LPS) treatment potentiated this effect and is C5aR dependent. Most important, DPSCs produced significantly higher levels of C5aR-mediated BDNF compared to BM-MSCs. Taken together, our data reveal novel roles for C5aR and inflammation in modulation of BDNF and NGF in DPSCs.
ISSN:	2045-2322 2045-2322