IFITM3 Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells by Modulating MAPK Signaling

Abstract

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.