Pathological and Transcriptomic Signatures of Tibial Dyschondroplasia and The Therapeutic Potential of Baicalin Via the CDH11/Wnt/β-Catenin Axis

Tibial dyschondroplasia (TD) is a prevalent skeletal disorder of rapidly growing broilers characterized by an avascular, non-mineralized cartilage plug in the proximal tibiotarsal growth plate and by failure of endochondral ossification; its genome-wide molecular signature and druggable nodes remain incompletely defined.This study integrated histopathology, micro-computed tomography, RNA sequencing and in-vivo and in-vitro genetic approaches to characterize the TD transcriptome and to determine whether baicalin, a flavone glucuronide from Scutellaria baicalensis, ameliorates TD through the cadherin-11 (CDH11)/Wnt/βcatenin axis.One-day-old Arbor Acres broilers (n = 240) were allocated to control (Con), TD, and baicalin (BA) groups; TD and BA birds received 100mg/kg thiram from d 4 to 7 and BA birds received 200mg/kg baicalin from d 8 to 18. TD birds exhibited growth plate thickening, an avascular cartilage plug, proteoglycan depletion, lameness and reduced growth.Baicalin reduced the TD incidence index by 58.4%, normalized growth plate architecture and restored trabecular bone volume.RNA-seq identified 2,847 differentially expressed genes (DEGs) between TD and Con, with gene ontology, KEGG and gene set enrichment analyses converging on suppression of Wnt/β-catenin signaling, chondrocyte differentiation and matrix organization; 66.4% of baicalin-responsive DEGs reverted toward control levels.Quantitative PCR confirmed coordinated suppression of CDH11, WNT3A and CTNNB1 with induction of GSK3B, MMP13, ADAMTS5 and CASP9 in TD, all reversed by baicalin.In primary chondrocytes, baicalin (20μM) reversed thiram-induced loss of viability, apoptosis and cell-cycle arrest; restored βcatenin nuclear translocation and TOPFlash reporter activity; and CDH11 knockdown abolished these effects.These findings identify suppression of CDH11dependent Wnt/β-catenin signaling as a central molecular signature of TD and demonstrate that baicalin is a therapeutically effective, pathway-targeted intervention within the 18-day experimental period.However, long-term effects on bone mechanical strength, persistence of recovery after treatment withdrawal, and practical dietary safety were not evaluated.Therefore, baicalin should be considered a promising candidate requiring further long-term validation before application in commercial broiler production.