AUTHOR=Gao Hui , Sun Tianyong , Yang Fanghong , Yuan Jiakan , Yang Mei , Kang Wenyan , Tang Di , Zhang Jun , Feng Qiang 

TITLE=The Pathogenic Effects of Fusobacterium nucleatum on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00807

DOI=10.3389/fcell.2020.00807

ISSN=2296-634X

ABSTRACT=<p>As one of the most common oral diseases, periodontitis is closely correlated with tooth loss in middle-aged and elderly people. <italic>Fusobacterium nucleatum</italic> (<italic>F. nucleatum</italic>) contributes to periodontitis, but the evidence in alveolar bone loss is still unclear. In this study, cytological experiments and transcriptome analyses were performed to characterize the biological process abnormalities and the molecular changes of <italic>F. nucleatum</italic>-stimulated osteoblasts. <italic>F. nucleatum</italic> could inhibit cell proliferation, promote cell apoptosis, and elevate pro-inflammatory cytokine production of osteoblasts, and it also inhibited osteoblast differentiation and mineralized nodule formation and decreased the expression of osteogenetic genes and proteins. Whole-transcriptome analyses identified a total of 235 transcripts that were differentially expressed in all six time points, most of which were inflammation-related genes. The genes, <italic>Ccl2</italic>, <italic>Ccl20</italic>, <italic>Csf1</italic>, <italic>Cx3cl1</italic>, <italic>Cxcl1</italic>, <italic>Cxcl3</italic>, <italic>Il6</italic>, <italic>Birc3</italic>, <italic>Map3k8</italic>, <italic>Nos2</italic>, <italic>Nfkb2</italic>, <italic>Tnfrsf1b</italic>, and <italic>Vcam1</italic>, played core roles in a PPI network, and interacted closely with other ones in the infection. In addition, 133 osteogenesis-related differential expression genes (DEGs) were time-serially dynamically changed in a short time-series expression miner (STEM) analysis, which were enriched in multiple cancer-related pathways. The core dynamic DEGs (<italic>Mnda</italic>, <italic>Cyp1b1</italic>, <italic>Comp</italic>, <italic>Phex</italic>, <italic>Mmp3</italic>, <italic>Tnfrsf1b</italic>, <italic>Fbln5</italic>, and <italic>Nfkb2</italic>) had been reported to be closely related to the development and metastasis in tumor and cancer progress. This study is the first to evaluate the long-term interaction of <italic>F. nucleatum</italic> on osteoblasts, which might increase the risk of cell carcinogenesis of normal osteoblasts, and provides new insight into the pathogenesis of bacterial-induced bone destruction.</p>