Chondroitin sulfate reverses tibial dyschondroplasia, broiler chondrocyte proliferation and differentiation dysfunction via the CHST11/β-Catenin pathway.

Abstract

Broiler tibial dyschondroplasia (TD) is a prevalent disorder that impairs locomotion and disrupts feeding behaviors, thereby compromising production efficiency and causing significant economic losses. Consequently, there is a growing need for effective therapeutic interventions. Chondroitin sulfate (CS) has demonstrated potential to enhance bone development and improve growth performance. However, the molecular mechanisms underlying CS alleviates TD remain unclear, due to its multiple biological activities. This study revealed that CS significantly alleviates TD in broilers by enhancing the body weight, increasing tibial mass, and promoting repair of growth plate injuries. Specifically, CS treatment restored the normal morphology of the tibial growth plate and upregulated the expression of extracellular matrix components (ECM), including Col2α1, ACAN, and CHST11, in TD-affected chondrocytes, consequently activating the Wnt/β-Catenin pathway. Notably, the inhibition of CHST11 markedly suppressed ECM synthesis and chondrocytes proliferation, accompanied by a decrease in β-Catenin expression, replicating the pathological patterns observed in thiram-induced TD chondrocytes. Importantly, CS supplementation effectively counteracted CHST11 inhibition, restoring ECM synthesis and cellular proliferation through the upregulation of the CHST11/β-Catenin pathway. These findings point to the pivotal role of CHST11-mediated activation of the Wnt/β-Catenin pathway plays a vital role in the therapeutic effect of CS in broiler TD.