RESUMEN
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.
Asunto(s)
Apoptosis , Fluoruros , Inflamación , Osteoblastos , Transducción de Señal , Humanos , Fluoruros/efectos adversos , Apoptosis/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Inflamación/inducido químicamente , Transducción de Señal/efectos de los fármacos , MicroARNs/metabolismo , MicroARNs/genética , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Mapas de Interacción de Proteínas , ARN Mensajero/metabolismo , ARN Mensajero/genética , Redes Reguladoras de Genes , Regulación de la Expresión Génica/efectos de los fármacos , Enfermedades Óseas/inducido químicamente , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
To explore the association between fluoride exposure and depression / anxiety in adults, the 1,169 participants were recruited. The demographic information of participants was obtained through questionnaire survey and physical measurements. Morning urine samples were collected, and urinary fluoride (UF) level was determined. Changes in depression and anxiety levels were evaluated using the Patient Health Questionnaire-2 and General Anxiety Disorder-2 scales. The association between psychiatric disorders and UF levels was analyzed. In the total population, the prevalence of depression and anxiety were 3.17% and 4.19%, respectively. These results showed no significant association between depression / anxiety scale scores and UF levels. Logistic regression suggested no significant association between depression / anxiety levels, and UF levels, but there was an interaction between UF and income on depression. Our findings highlighted the interaction between fluoride exposure and monthly income, which may affect depression in adults.