Related Experiment Video
Updated: Jan 13, 2026
Murine Model of Advanced Periodontitis Induced by Nylon Ligature in the Second Upper Molar
Published on: May 30, 2025
Integrative Human Genomic and Pharmacological Analyses Identify CACNB4 as a Druggable Target for Periodontitis
Yixuan Jiang1,2, Zhengyu Guan1,2, Xiu Yao3,4
1Department of Stomatology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Aim:
To identify and validate druggable gene targets for periodontitis using integrative human genomic analyses and to explore their therapeutic potential through pharmacological evaluation.
Methods:
To identify therapeutic targets for periodontitis, we performed Mendelian randomization (MR) and colocalization analyses using the cis-expression quantitative trait loci (cis-eQTL) data of druggable genes and genome-wide association studies (GWAS) data. This approach allowed us to pinpoint druggable gene targets significantly associated with periodontitis, which were then validated by immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Next, we applied drug prediction and molecular docking to identify candidate drugs for the key druggable target. Finally, pharmacological analyses were conducted to evaluate the efficacy of these drugs in vitro and in vivo.
Results:
A total of six genes (CACNB4, PSMA4, GAA, FGF2, AURKAIP1, and ADAM12) were found to be causally associated with periodontitis in the MR analysis, of which two (CACNB4 and PSMA4) were further supported by colocalization analyses. CACNB4 was significant in both cohorts in MR analysis and supported by localization and experimental evidence. Moreover, the reliability of this target was confirmed in patient samples. We then identified drugs with repurposing potential that target CACNB4, namely verapamil and safinamide. Pharmacological analyses showed that both agents attenuated osteoclast differentiation, indicating therapeutic potential. Importantly, validation at the cellular level confirmed the activity of these candidate drug targets.
Conclusion:
Through MR analysis, we identified CACNB4 as a potential druggable gene for periodontitis. Among the drugs targeting CACNB4, verapamil and safinamide emerged as the most promising candidates for periodontitis treatment. Pharmacological studies further demonstrated that these agents may inhibit osteoclast differentiation by targeting CACNB4, thereby offering potential therapeutic options for periodontitis.
Insights
New research identifies CACNB4 as a potential target for periodontitis treatment. Drug repurposing identified verapamil and safinamide as promising candidates to inhibit osteoclast differentiation and halt disease progression.
Area of Science:
- Genetics
- Pharmacology
- Periodontal disease research
Background:
- Periodontitis lacks effective treatments to halt progression, with current therapies managing symptoms.
- Drug repurposing offers a rapid strategy for discovering novel and effective periodontitis treatments.
Purpose of the Study:
- To identify druggable gene targets for periodontitis using Mendelian randomization (MR) and colocalization analyses.
- To discover potential drug candidates for periodontitis through drug prediction and molecular docking.
Main Methods:
- Utilized MR and cis-expression quantitative trait loci (cis-eQTL) data to identify genes associated with periodontitis.
- Validated gene targets using immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR).
- Employed drug prediction and molecular docking to identify candidate drugs, followed by in vitro and in vivo pharmacological analyses.
Main Results:
- Identified six genes causally associated with periodontitis, with CACNB4 and PSMA4 supported by colocalization.
- CACNB4 was confirmed as a reliable target in patient samples.
- Verapamil and safinamide were identified as potential drugs targeting CACNB4, showing efficacy in attenuating osteoclast differentiation.
Conclusions:
- CACNB4 is a promising druggable target for periodontitis.
- Verapamil and safinamide show potential for periodontitis treatment by targeting CACNB4.
- These drugs may inhibit osteoclast differentiation, offering new therapeutic avenues for periodontitis.
