Apoptosis and Inflammation Involved with Fluoride-Induced Bone Injuries

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.