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Apoptosis and Inflammation Involved with Fluoride-Induced Bone Injuries
Miao Wang1, Kangting Luo1, Tongtong Sha1
1School of Public Health, Zhengzhou University, Zhengzhou 450001, China.
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.
Insights
Excessive fluoride exposure causes skeletal fluorosis by affecting bone cells. This study identifies key genes and signaling pathways, including PI3K-Akt, IL-17, and TGF-beta, involved in bone injury pathogenesis.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Excessive fluoride exposure is a known cause of skeletal fluorosis.
- The precise molecular mechanisms underlying fluoride-induced bone injury remain poorly understood.
- Identifying these mechanisms is crucial for developing targeted therapeutic strategies.
Purpose of the Study:
- To elucidate the pathogenesis of fluoride-induced bone injuries.
- To identify key genes, regulatory networks, and signaling pathways involved in skeletal fluorosis.
- To predict potential pharmacological targets for treating fluoride-induced bone damage.
Main Methods:
- Systematic literature search for genes associated with fluoride-induced bone injury.
- Gene enrichment analyses (functional and pathway analysis).
- Construction of transcription factor-mRNA-microRNA (TF-mRNA-miRNA) and protein-protein interaction (PPI) networks.
- Screening of key protein expression using the Human Protein Atlas (HPA) database.
- Prediction of candidate pharmacological targets using the Drug Signature Database.
Main Results:
- Identified 112 osteoblast, 35 osteoclast, and 41 chondrocyte-related differentially expressed genes (DEGs) from 85 studies.
- Significantly enriched pathways include PI3K-Akt (osteoblasts), IL-17 (osteoclasts), and TGF-beta (chondrocytes).
- Key regulatory genes identified include Col1a1, Bcl2, Fgfr1, Mmp9, Mmp13, Bmp2, and Bmp7.
- Predicted potential drugs for skeletal fluorosis: Selenium methyl cysteine, CGS-27023A, and calcium phosphate.
Conclusions:
- The PI3K-Akt signaling pathway is implicated in osteoblast apoptosis in fluoride-induced bone injury.
- The IL-17 and TGF-beta signaling pathways are involved in osteoclast and chondrocyte inflammation, respectively.
- These findings provide insights into the molecular mechanisms of skeletal fluorosis and suggest potential therapeutic avenues.
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