PDF(Pubmed)
Abstract：
BACKGROUND: Excessive fluoride exposure induces skeletal fluorosis, but the specific mechanism responsible is still unclear. Therefore, this study aimed to identify the pathogenesis of fluoride-induced bone injuries.
METHODS: We systematically searched fluoride-induced bone injury-related genes from five databases. Then, these genes were subjected to enrichment analyses. A TF (transcription factor)-mRNA-miRNA network and protein-protein interaction (PPI) network were constructed using Cytoscape, and the Human Protein Atlas (HPA) database was used to screen the expression of key proteins. The candidate pharmacological targets were predicted using the Drug Signature Database.
RESULTS: A total of 85 studies were included in this study, and 112 osteoblast-, 35 osteoclast-, and 41 chondrocyte-related differential expression genes (DEGs) were identified. Functional enrichment analyses showed that the Atf4, Bcl2, Col1a1, Fgf21, Fgfr1 and Il6 genes were significantly enriched in the PI3K-Akt signaling pathway of osteoblasts, Mmp9 and Mmp13 genes were enriched in the IL-17 signaling pathway of osteoclasts, and Bmp2 and Bmp7 genes were enriched in the TGF-beta signaling pathway of chondrocytes. With the use of the TF-mRNA-miRNA network, the Col1a1, Bcl2, Fgfr1, Mmp9, Mmp13, Bmp2, and Bmp7 genes were identified as the key regulatory factors. Selenium methyl cysteine, CGS-27023A, and calcium phosphate were predicted to be the potential drugs for skeletal fluorosis.
CONCLUSIONS: These results suggested that the PI3K-Akt signaling pathway being involved in the apoptosis of osteoblasts, with the IL-17 and the TGF-beta signaling pathways being involved in the inflammation of osteoclasts and chondrocytes in fluoride-induced bone injuries.
METHODS: We systematically searched fluoride-induced bone injury-related genes from five databases. Then, these genes were subjected to enrichment analyses. A TF (transcription factor)-mRNA-miRNA network and protein-protein interaction (PPI) network were constructed using Cytoscape, and the Human Protein Atlas (HPA) database was used to screen the expression of key proteins. The candidate pharmacological targets were predicted using the Drug Signature Database.
RESULTS: A total of 85 studies were included in this study, and 112 osteoblast-, 35 osteoclast-, and 41 chondrocyte-related differential expression genes (DEGs) were identified. Functional enrichment analyses showed that the Atf4, Bcl2, Col1a1, Fgf21, Fgfr1 and Il6 genes were significantly enriched in the PI3K-Akt signaling pathway of osteoblasts, Mmp9 and Mmp13 genes were enriched in the IL-17 signaling pathway of osteoclasts, and Bmp2 and Bmp7 genes were enriched in the TGF-beta signaling pathway of chondrocytes. With the use of the TF-mRNA-miRNA network, the Col1a1, Bcl2, Fgfr1, Mmp9, Mmp13, Bmp2, and Bmp7 genes were identified as the key regulatory factors. Selenium methyl cysteine, CGS-27023A, and calcium phosphate were predicted to be the potential drugs for skeletal fluorosis.
CONCLUSIONS: These results suggested that the PI3K-Akt signaling pathway being involved in the apoptosis of osteoblasts, with the IL-17 and the TGF-beta signaling pathways being involved in the inflammation of osteoclasts and chondrocytes in fluoride-induced bone injuries.
摘要：
背景：过量的氟暴露会导致氟骨症，但具体机制尚不清楚。因此,本研究旨在明确氟诱导骨损伤的发病机制。
方法：我们从五个数据库中系统地搜索了氟化物诱导的骨损伤相关基因。然后，这些基因进行了富集分析。使用Cytoscape构建TF(转录因子)-mRNA-miRNA网络和蛋白-蛋白相互作用(PPI)网络,人蛋白图谱(HPA)数据库用于筛选关键蛋白的表达。使用药物标签数据库预测候选药理学靶标。
结果：本研究共纳入85项研究，和112个成骨细胞，35破骨细胞-，并鉴定出41个软骨细胞相关差异表达基因(DEGs)。功能富集分析表明,Atf4、Bcl2、Col1a1、Fgf21、Fgfr1和Il6基因在成骨细胞PI3K-Akt信号通路中显著富集,Mmp9和Mmp13基因富集在破骨细胞的IL-17信号通路中,和Bmp2和Bmp7基因富集在软骨细胞的TGF-β信号通路中。随着TF-mRNA-miRNA网络的使用，Col1a1、Bcl2、Fgfr1、Mmp9、Mmp13、Bmp2和Bmp7基因被确定为关键调控因子。硒甲基半胱氨酸，CGS-27023A,和磷酸钙被预测为治疗氟骨症的潜在药物。
结论：这些结果表明PI3K-Akt信号通路参与了成骨细胞的凋亡，IL-17和TGF-β信号通路参与了氟化物诱导的骨损伤中破骨细胞和软骨细胞的炎症。
方法：我们从五个数据库中系统地搜索了氟化物诱导的骨损伤相关基因。然后，这些基因进行了富集分析。使用Cytoscape构建TF(转录因子)-mRNA-miRNA网络和蛋白-蛋白相互作用(PPI)网络,人蛋白图谱(HPA)数据库用于筛选关键蛋白的表达。使用药物标签数据库预测候选药理学靶标。
结果：本研究共纳入85项研究，和112个成骨细胞，35破骨细胞-，并鉴定出41个软骨细胞相关差异表达基因(DEGs)。功能富集分析表明,Atf4、Bcl2、Col1a1、Fgf21、Fgfr1和Il6基因在成骨细胞PI3K-Akt信号通路中显著富集,Mmp9和Mmp13基因富集在破骨细胞的IL-17信号通路中,和Bmp2和Bmp7基因富集在软骨细胞的TGF-β信号通路中。随着TF-mRNA-miRNA网络的使用，Col1a1、Bcl2、Fgfr1、Mmp9、Mmp13、Bmp2和Bmp7基因被确定为关键调控因子。硒甲基半胱氨酸，CGS-27023A,和磷酸钙被预测为治疗氟骨症的潜在药物。
结论：这些结果表明PI3K-Akt信号通路参与了成骨细胞的凋亡，IL-17和TGF-β信号通路参与了氟化物诱导的骨损伤中破骨细胞和软骨细胞的炎症。
