BMP8A/TGF-β1 regulates chicken chondrocyte proliferation, differentiation, and apoptosis induced by Thiram.

Abstract

Objective: Tibial dyschondroplasia (TD) is a metabolic cartilage disorder that impairs the development of the tibial growth plate in rapidly growing poultry. This study aimed to identify key genes and clarify the molecular mechanisms involved in tibial dyschondroplasia (TD) in broiler chickens. It also evaluated the potential effect of vitamin D3 (VD3) in alleviating TD symptoms, focusing particularly on the role of BMP8A and its interaction with transforming growth factor-β1 (TGF-β1).

Methods: 94 broiler chicks were divided into three groups: healthy control, thiram-induced TD, and thiram-induced with VD3 supplementation. RNA sequencing was performed to identify differentially expressed genes (DEGs) across groups. Target genes were further validated using molecular biology techniques, including gene expression analysis and in vitro functional assays on chondrocytes.

Results: VD3 effectively mitigated thiram-induced chondrocyte damage. RNA-seq revealed 625 DEGs enriched in pathways such as the TGF-β signaling pathway. Four co-differentially expressed genes (BMP8A, COL10A1, SDC3, and SCIN) were closely associated with collagen metabolism and reorganization. Functional assays, such as CCK8, EdU and IHC showed that BMP8A mitigated collagen accumulation induced by elevated TGF-β1 levels, promoted the release of collagen types I, II, and X, and facilitated chondrocyte proliferation and differentiation while reducing apoptosis.

Conclusion: BMP8A plays a protective role in TD by regulating collagen balance and maintaining chondrocyte function, especially under high TGF-β1 conditions. VD3 supplementation effectively reduces TD-related damage. The interaction between BMP8A and TGF-β1 may provide a novel therapeutic target for preventing and treating TD in poultry.