Thiram exposure induces tibial dyschondroplasia in broilers via the regulation effect of circ_003084/miR-130c-5p/BMPR1A crosstalk on chondrocyte proliferation and differentiation
Hengyong Xu, Yuru Jiang, Yuxiang Lu, Zhi Hu, Ranran Du, Yuxin Zhou, Yiping Liu, Xiaoling Zhao, Yaofu Tian, Chaowu Yang, Zengrong Zhang, Mohan Qiu, Yan Wang
Abstract
Thiram, an agricultural insecticide, has been demonstrated to induce tibial dyschondroplasia (TD) in avian species. Circular RNA (circRNAs), a novel class of functional biological macromolecules characterized by their distinct circular structure, play crucial roles in various biological processes and diseases. Nevertheless, the precise regulatory mechanism underlying non-coding RNA involvement in thiram-induced broiler tibial chondrodysplasia remains elusive. In this study, we established a broiler model of thiram exposure for 10 days to assess TD and obtain a ceRNA network by RNA sequencing. By analyzing the differentially expressed circRNAs network, we id entify that circ_003084 was significantly upregulated in TD cartilage. Elevated circ_003084 inhibited TD chondrocytes proliferation and differentiation in vitro but promote apoptosis. Mechanistically, circ_003084 competitively binds to miR-130c-5p and prevents miR-130c-5p to decrease the level of BMPR1A, which upregulates the expression of apoptosis genes Caspase 3, Caspase 9, Bax and Bcl2, and finally facilitates cell apoptosis. Taken together, these findings imply that circ_003084/miR-130c-5p/BMPR1A interaction regulated TD chicken chondrocyte proliferation, apoptosis, and differentiation. This is the first work to reveal the mechanism of regulation of circRNA-related ceRNA on thiram-induced TD, offering a key reference for environmental toxicology. Thiram, a widely utilized pesticide in agriculture, exhibits promising efficacy in enhancing crop yields and mitigating disease; however, improper usage and handing can result in contamination of soil, groundwater, vegetable, and food. Consequently, it poses a serious threat to animal health and food safety. However, it is not clear how thiram regulates tibial dyschondroplasia (TD) occurrence via the circRNA’s ceRNA axis. Here, we investigated the effects of thiram exposure on circRNA expression profiles in chicken chondrocytes, and revealed that circ_003084 functions as a miRNA sponge to directly sequester miR-130c-5p from the BMPR1A gene, thereby promoting BMPR1A mRNA expression post-transcription and ultimately inhibiting the proliferation and differentiation of TD chondrocyte. This work provides seminal data and research idea for investigating the toxic mechanism of ncRNA involvement in thiram-induced dyschondroplasia in chickens.