10 / 2024-10-07 13:33:43

Cant1/β-Catenin mediated chondrocyte extracellular matrix biosynthesis dysfunction in tibial dyschondroplasia broiler

Broiler tibial chondrodysplasia (TD) is a cartilage metabolic disease featuring cartilage development disorders and extracellular matrix (ECM) biosynthesis dysfunction. Although our previous finding showed that Cant1 and Wnt/β-Catenin signaling pathways are highly associated with TD occurrence, but the signaling pathways' transmission relationship aspects are ill-defined. Here we show that thiram-induced TD suppressed the expression of matrix proteins ACAN and Col2a1 and induce ECM biosynthesis dysfunction phenotype in broiler chondrocytes. Further, thiram-induced TD inhibited Cant1 protein, and Wnt/β-Catenin signaling transmission disrupted the expression of β-Catenin. Overexpressed Cant1 in primary broiler chondrocytes up-regulated the expression of CHST11, CHSY1, and CHPF mRNA which mediated ECM biosynthesis by enhancing the β-Catenin expression. Correspondingly, silenced Cant1 obtained the contrary consequence. The Cant1 overexpression resulting in increased ECM biosynthesis can be further boosted by activating Wnt/β-Catenin signaling transmission or restrained by blocking the signal transmission. Moreover, the double immunofluorescence labeling and Cant1-Flag fusion protein pull-down assay revealed that the Cant1 interacted with the β-Catenin protein from the Wnt/β-Catenin signaling pathway, and the co-localization analysis showed the expression of Cant1 and β-Catenin are positive correlated. Taken together, the Cant1/β-Catenin axis regulates broiler chondrocyte ECM biosynthesis and broiler TD development, and targeted interventions may provide therapeutic and preventive approaches in broiler TD.