Inhibitory effect and mechanism of herbicide flurochloridone on osteogenic differentiation
10.19428/j.cnki.sjpm.2025.250072
- VernacularTitle:农药氟咯草酮抑制成骨分化作用和机制
- Author:
Liming XUE
1
;
Jiale XU
1
;
Zhaofu MENG
2
;
Zhijun ZHOU
2
;
Dasheng LU
1
;
Guoquan WANG
1
Author Information
1. Division of Chemical Toxicity and Safety Assessment, State Environmental Protection Key Laboratory of Environmental Health Impact Assessment of Emerging Contaminants, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 201107, China
2. School of Public Health, Fudan University, Shanghai 200032, China
- Publication Type:Journal Article
- Keywords:
flurochloridone;
osteoblast;
osteogenic differentiation;
gene chip technique;
BMP/SMAD pathway
- From:
Shanghai Journal of Preventive Medicine
2025;37(12):1003-1008
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the role of flurochloridone (FLC) on osteogenic differentiation and the potential mechanism of inhibiting bone formation, and to provide new insights into bone health risks associated with FLC pesticide exposure. MethodsNeonatal rat skull differentiation primary osteoblast model was used to investigate the effects of 1, 10 and 100 μmol·L-1 FLC exposure on cell viability, osteogenic differentiation alkaline phosphatase (ALP) activity, and bone mineralization nodule formation, respectively. The potential mechanism underlying the inhibition of FLC on osteoblast differentiation was analyzed using osteogenic differentiation gene chip technique, and the expression of key genes and proteins in the pathway was validated using reverse transcription polymerase chain reaction (RT-PCR) and protein immunoblotting (Western blot) methods. ResultsExposure to FLC at a concentration of 100 μmol·L⁻¹ reduced cell proliferation, ALP activity, and the formation of mineralized nodules in primary osteoblasts. Gene chip analyses revealed that exposure to 10 μmol·L⁻¹ FLC induced 15 differentially expressed genes (DEGs). Among these, MMP9 and Tnf were up-regulated, while Nkx3⁃2, Tuft1, Bmp2, Col12a1, Pparg, Enam, Igf1, Bmp5, Bmp3, Calcr, Egf, Igfbp3, and Col14a1 were down-regulated. Results of protein-protein interaction analyses and gene ontology enrichment analyses indicated that FLC inhibited the BMP/SMAD pathway involved in osteogenic differentiation. FLC suppressed the protein expression of BMP2 and Osterix, as well as the expression of key genes critical for osteogenic differentiation and ossification, such as BMP2, Runx2, SMAD1, and SMAD5 in the BMP/SMAD pathway. ConclusionFLC affects osteogenic differentiation and bone formation potential by regulating the BMP/SMAD axis and the expression of osteogenic genes, suggesting its potential risk in bone metabolism.
