Kim, Myungsuk Lim, Jisun Lee, Jung-Hee Lee, Kyung-Mi Kim, Suji Park, Kye Won Nho, Chu Won Cho, Yoon Shin 2024-01-19T23:32:14Z 2024-01-19T23:32:14Z 2021-09-03 2018-02 2045-2322 https://pubs.kist.re.kr/handle/201004/121760 Genistein, a phyto-estrogen, can potentially replace endogenous estrogens in postmenopausal women, but the underlying molecular mechanisms remain incompletely understood. To obtain insight into the effect of genistein on bone differentiation, RNA sequencing (RNA-seq) analysis was used to detect differentially expressed genes (DEGs) in genistein-treated vs. untreated MC3T3-E1 mouse osteoblastic cells. Osteoblastic cell differentiation was monitored by measuring osteoblast differentiation factors (ALP production, bone mineralization, and expression of osteoblast differentiation markers). From RNA-seq analysis, a total of 132 DEGs (including 52 up-regulated and 80 down-regulated genes) were identified in genistein-treated cells (FDR q-value < 0.05 and fold change > 1.5). KEGG pathway and Gene Ontology (GO) enrichment analyses were performed to estimate the biological functions of DEGs and demonstrated that these DEGs were highly enriched in functions related to chemotactic cytokines. The functional relevance of DEGs to genistein-induced osteoblastic cell differentiation was further evaluated by siRNA-mediated knockdown in MC3T3-E1 cells. These siRNA knockdown experiments (of the DEGs validated by real-time qPCR) demonstrated that two up-regulated genes (Ereg and Efcab2) enhance osteoblastic cell differentiation, while three down-regulated genes (Hrc, Gli, and Ifitm5) suppress the differentiation. These results imply their major functional roles in bone differentiation regulated by genistein. English Nature Publishing Group Understanding the functional role of genistein in the bone differentiation in mouse osteoblastic cell line MC3T3-E1 by RNA-seq analysis Article 10.1038/s41598-018-21601-9 1 Scientific Reports, v.8 Scientific Reports 8 Y scie scopus 000425380900040 2-s2.0-85042217162 Multidisciplinary Sciences Science & Technology - Other Topics Article LEUKEMIA INHIBITORY FACTOR GENE-EXPRESSION SIGNALING PATHWAY MECHANISMS PHYTOESTROGENS IDENTIFICATION ACTIVATION genistein MC3T3-E1 RNA-seq bone differentiation