Assessing the effect and related mechanism of naringenin on the proliferation, osteogenic differentiation and endothelial differentiation of human periodontal ligament stem cells

Naringenin (NAR) is a natural flavonoid which exerts extensive biological activity, including anti-oxidation, anti-inflammation, anti-cancer, immune regulation and so on. However, the effect and mechanism of NAR in the alveolar bone regeneration are still unclear, which limits its clinical use. Hence, we investigated the effects of NAR in the proliferation, osteogenic and endothelial differentiation of human periodontal ligament stem cells (hPDLSCs) and explore the possible mechanism. The results showed that the proper concentrations (100 nM-10 μM) of NAR can promote the proliferation rate, osteogenic and endothelial differentiation of hPDLSCs. And the 1 μM NAR had the best proliferation promoting effect, while the 10 μM NAR had the best ability of promoting osteogenic and endothelial differentiation. NAR also promoted the mRNA expression of SDF-1 in a concentration dependent manner in PDLSCs. After adding the selective CXCR4 Antagonist AMD3100, the osteogenic effect of NAR on PDLSCs is slightly enhanced, while the endothelial differentiation effect of NAR on hPDLSCs is attenuated. In summary, these results indicated that NAR promoted the proliferation of hPDLSCs, and promoted endothelial differentiation of hPDLSCs via SDF-1 to activate SDF-1/CXCR4 signaling pathway. However, the mechanism of which SDF-1 related signaling pathway is activated by NAR to enhance the osteogenic differentiation of hPDLSCs still needs to be investigated.