Dental pulp stem cells (DPSCs) invoke wide interest due to their roles in in dentin regeneration and repair, and more research is required to illustrate the molecular basis. In this study, we induced osteogenic differentiation in human DPSCs to investigate the role of interferon-induced transmembrane (IFITM) family in osteogenic differentiation. Our results demonstrated that genes of the IFITM family, IFITM1, IFITM3, and IFITM5 were upregulated during the osteogenic differentiation of DPSCs. Loss-of-function and gain-of-function assays indicated that IFITM3 knockdown suppressed osteogenic differentiation, assessed by the reduction of alkaline phosphatase (ALP) activity, nodule mineralization, and the expressions of several osteogenic differentiation-associated genes; in contrast, IFITM3 overexpression increased ALP activity, nodule mineralization, and the expressions of osteogenic differentiation-associated genes. Further investigation revealed that IFITM3 was involved in the regulation of mitogen-activated protein kinase (MAPK) signaling during osteogenic differentiation, and pharmacological inhibition of both ERK and p38 suppressed the effects of IFITM3 overexpression in osteogenic differentiation. These results suggest that IFITM3 promotes osteogenic differentiation of DPSCs by regulating MAPK signaling. Our findings enhance the existing knowledge on the role of IFITM family in osteogenic differentiation and the molecular basis of IFITM3.
Stress has been proven to modulate an individual’s immune system through the release of pituitary and adrenal hormones such as the catecholamines, growth hormone, and glucocorticoids. These signal molecules can significantly alter the host immune system and make it susceptible to viral infection. In this study, we investigate whether epigoitrin, a natural alkaloid from Isatis indigotica, provides protection against influenza infection by reducing the host’s susceptibility to influenza virus under stress and its underlying mechanism. To support it, the mouse restraint stress model and the corticosterone-induced stress model were employed. Our results demonstrated that epigoitrin significantly decreased the susceptibility of restraint mice to influenza virus, evidenced by lowered mortality, attenuated inflammation, and decreased viral replications in lungs. Further results revealed that epigoitrin reduced the protein expression of mitofusin-2 (MFN2), which elevated mitochondria antiviral signaling (MAVS) protein expression and subsequently increased the production of IFN-β and interferon inducible transmembrane 3 (IFITM3), thereby helping to fight viral infections. In conclusion, our study indicated that epigoitrin could reduce the susceptibility to influenza virus via mitochondrial antiviral signaling.
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