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Interference with SPARC inhibits Benzophenone-3 induced ferroptosis in osteoarthritis: Evidence from bioinformatics
Yaoyao Nie1, Houpu Liu1, Runtao Wu1
1Department of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical College, Hangzhou 310053, China.
Abstract:
The aim of this study is to conduct a thorough evaluation of the association between Benzophenone-3 (BP-3) exposure and OA, offering critical insights into the underlying mechanisms involved. The National Health and Nutrition Examination Survey (NHANES) database was utilized to investigate the correlation between BP-3 and osteoarthritis. Proteomic sequencing from clinical sample and the PharmMapper online tool were employed to predict the biological target of BP-3. Cellular molecular assays and transfection studies were performed to verify the prediction from bioinformatics analyses. Through cross-sectional analysis of the NHANES database, we identified BP-3 as a risk factor for OA development. The results of proteomic sequencing showed that Secreted Protein Acidic and Rich in Cysteine (SPARC) was significantly elevated in the area of damage compared to the undamaged area. SPARC was also among the potential biological targets of BP-3 predicted by the online program. Through in vitro cell experiments, we further determined that the toxicological effects of BP-3 may be due to SPARC, which elevates intracellular GPX4 levels, activates the glutathione system, and promotes lipid peroxidation to mitigate ferroptosis. Inhibiting SPARC expression has been shown to reduce inflammation and ferroptosis in OA contexts. This research provides an expansive understanding of BP-3's influence on osteoarthritis development. We have identified SPARC as a potent target for combating chondrocyte ferroptosis in BP-3-associated osteoarthritis.
Insights
Benzophenone-3 (BP-3) exposure is a risk factor for osteoarthritis (OA). BP-3 promotes OA by increasing Secreted Protein Acidic and Rich in Cysteine (SPARC), which mitigates ferroptosis in chondrocytes.
Area of Science:
- Environmental Health
- Biochemistry
- Orthopedics
Background:
- Benzophenone-3 (BP-3) is a common UV filter with potential endocrine-disrupting properties.
- Osteoarthritis (OA) is a prevalent degenerative joint disease with complex etiologies.
- The link between environmental chemical exposure and OA pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the association between Benzophenone-3 (BP-3) exposure and osteoarthritis (OA).
- To elucidate the underlying molecular mechanisms by which BP-3 may contribute to OA development.
- To identify potential therapeutic targets for BP-3-induced OA.
Main Methods:
- Cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) database.
- Proteomic sequencing of clinical samples to identify differentially expressed proteins.
- Bioinformatic prediction of BP-3's biological targets using PharmMapper.
- In vitro cellular assays to validate predicted molecular mechanisms.
Main Results:
- BP-3 exposure was identified as a significant risk factor for OA development in the NHANES cohort.
- Secreted Protein Acidic and Rich in Cysteine (SPARC) was found to be elevated in damaged OA tissues and predicted as a BP-3 target.
- BP-3 exposure increased intracellular GPX4 levels via SPARC, activating the glutathione system and promoting lipid peroxidation to inhibit ferroptosis.
Conclusions:
- BP-3 exposure is associated with an increased risk of osteoarthritis.
- The mechanism involves BP-3-induced elevation of SPARC, leading to altered cellular responses and ferroptosis mitigation in chondrocytes.
- SPARC presents a potential therapeutic target for mitigating ferroptosis in BP-3-associated OA.
