Potential molecular links between triclosan exposure and osteoarthritis: An integrative systems toxicology study
Abstract
Osteoarthritis (OA) is a chronic disease affecting the entire joint, influenced by a combination of inflammatory, metabolic, immune, and environmental factors. Triclosan (TCS), a commonly used antimicrobial compound, has been linked to oxidative and immune disturbances; however, its molecular relevance to OA remains to be elucidated. This study integrated network toxicology, bulk transcriptomics, cross-cohort machine learning prioritization, immune infiltration analysis, single-cell transcriptomic analysis, molecular docking, molecular dynamics simulations, and primary chondrocyte experiments. Thirty candidate genes related to both TCS and OA were identified, with CBR3, MAOA, MMP13, and AVPR1A being prioritized. Among these, CBR3 exhibited the most stable contribution to model predictions, widespread expression across OA chondrocyte subpopulations, and significant associations with inferred immune-cell composition. Supporting molecular docking and dynamics analyses indicated structural compatibility and dynamic feasibility between TCS and the four candidate proteins. In primary rat chondrocytes, low-dose TCS heightened reactive oxygen species (ROS) accumulation, upregulated Cbr3 and Mmp13, downregulated Col2a1, Maoa, and Avpr1a, and increased CBR3 protein levels, with specific redox-related and matrix-related alterations becoming more pronounced under IL-1β stimulation. These findings contribute to a model that links TCS-associated redox disturbances to OA-relevant chondrocyte stress and matrix remodeling, providing candidate molecular connections for future mechanistic validation.
Related
- Integrative network toxicology and machine learning reveal the potential role of 5-hydroxymethylfurfural in exacerbating pulmonary fibrosis
- Investigating potential molecular mechanisms linking 6PPD-quinone exposure to Intervertebral Disc Degeneration: A network toxicology, molecular docking, and molecular dynamics simulation study
- Damage-Associated Molecular Patterns and Trained Immunity of Monocyte-Macrophage Populations in Osteoarthritis: Potential Molecular Links and Therapeutic Opportunities.
- Integrative network pharmacology, machine learning, and experimental validation reveal the protective potential and potential molecular mechanisms of orientin in DSS-induced colitis
- Genetic-multi-omics causal inference coupled with integrative in-vitro toxicology reveals immune-metabolite mediators for aortic aneurysm risk
BibTeX
@article{tang2026potential,
title = {{Potential molecular links between triclosan exposure and osteoarthritis: An integrative systems toxicology study}},
author = {Xijie Tang and Haijia Xu and Xiangzhong Liu and Yi Yang and Zhanghua Li},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117868},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03251-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Potential molecular links between triclosan exposure and osteoarthritis: An integrative systems toxicology study
AU - Xijie Tang
AU - Haijia Xu
AU - Xiangzhong Liu
AU - Yi Yang
AU - Zhanghua Li
PY - 2026
DA - 2026/10/13
JO - iScience
DO - 10.1016/j.isci.2026.117868
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03251-7
AB - Osteoarthritis (OA) is a chronic disease affecting the entire joint, influenced by a combination of inflammatory, metabolic, immune, and environmental factors. Triclosan (TCS), a commonly used antimicrobial compound, has been linked to oxidative and immune disturbances; however, its molecular relevance to OA remains to be elucidated. This study integrated network toxicology, bulk transcriptomics, cross-cohort machine learning prioritization, immune infiltration analysis, single-cell transcriptomic analysis, molecular docking, molecular dynamics simulations, and primary chondrocyte experiments. Thirty candidate genes related to both TCS and OA were identified, with CBR3, MAOA, MMP13, and AVPR1A being prioritized. Among these, CBR3 exhibited the most stable contribution to model predictions, widespread expression across OA chondrocyte subpopulations, and significant associations with inferred immune-cell composition. Supporting molecular docking and dynamics analyses indicated structural compatibility and dynamic feasibility between TCS and the four candidate proteins. In primary rat chondrocytes, low-dose TCS heightened reactive oxygen species (ROS) accumulation, upregulated Cbr3 and Mmp13, downregulated Col2a1, Maoa, and Avpr1a, and increased CBR3 protein levels, with specific redox-related and matrix-related alterations becoming more pronounced under IL-1β stimulation. These findings contribute to a model that links TCS-associated redox disturbances to OA-relevant chondrocyte stress and matrix remodeling, providing candidate molecular connections for future mechanistic validation.
SN - 2589-0042
ER -