Avermectin reduces bone mineralization via the TGF-β signaling pathway in zebrafish

Avermectin, a widely used insecticide, is primarily effective against animal parasites and insects. Given its extensive application in agriculture, a large amount of avermectin accumulates in natural water bodies. Studies have shown that avermectin has significant toxic effects on various organisms and on the nervous system, spine, and several other organs in humans. However, the effects of avermectin on bone development have not been reported yet. In this study, zebrafish embryos were treated with different concentrations of avermectin to explore the effects of avermectin on early bone development. The results showed that avermectin disturbed early bone development in zebrafish, caused abnormal craniofacial chondrogenesis, and reduced bone mineralization. Avermectin treatment significantly reduced mineralization in zebrafish scales and increased osteoclast activity. Real-time quantitative PCR results showed that avermectin decreased the expression of genes related to osteogenesis and transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) signaling pathways. The TGF-β inhibitor SB431542 rescued avermectin-induced bone mineralization and osteogenesis related gene expression in zebrafish during early development. Thus, this study provides insight into the mechanism of damage caused by avermectin on bone development, thus helping demonstrate its toxicity.