Effect of Zika virus on the osteogenic capacity of mesenchymal stem cells via the Notch signaling pathway

Abstract

Background: Zika virus is a small enveloped flavivirus transmitted through the bite of the aedes mosquitos. Epidemiologic survey has shown that diseases caused by Zika virus mainly include microcephaly and malformation of cranial bones.In 2016, nucleic acid screening for the zika virus was conducted in Puerto Rico, and the results indicated that the seasonal incidence rate of zika virus could reach 21.1%. Research Purpose: To investigate the effect of zika virus on the osteogenic capacity of mesenchymal stem cells. Method: We induced the zika virus-infected human mesenchymal stem cells into osteoblasts. Real-time quantitative polymerase chain reaction and Western Blot were used to detect the mRNA and protein expression of the osteogenic markers, as well as notch signaling pathway molecules. A γ-secretase inhibitor was used to explore whether the osteogenic ability of Zika virus-infected mesenchymal stem cells is restored after inhibiting the notch signaling pathway. Establish a mouse model to verify the results in vivo. Result: We found that zika virus activated the Notch signaling pathway in mesenchymal stem cells,hindering the formation of osteoblasts. After treating mesenchymal stem cells with the gamma-secretase inhibitor,the osteogenic ability of mesenchymal stem cells can be restored. The same results were observed in the mouse model. Conclusion: Zika virus suppresses the osteogenic capacity of mesenchymal stem cells via notch signaling pathway.