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Abstract
Bacterial Chondronecrosis and Osteomyelitis (BCO) is a leading cause of lameness in modern broiler chickens, imposing substantial welfare and economic concerns on the poultry industry. The pathophysiological mechanisms behind BCO and experimental models of the disease remain poorly defined. This thesis systematically investigates the multifactorial etiology of BCO besides highlighting pathogen-induced osteoimmune dysregulation, gut-bone axis, and possible mitigation strategies. To elucidate the roles of Staphylococcus aureus and lipopolysaccharides (LPS) in induction and progression of BCO, a series of in vivo and in vitro studies were conducted. Invitro and embryonic models using LPS exposure revealing disruption of osteogenic differentiation in chicken mesenchymal stem cells (MSCs). Furthermore, MSCs and macrophage -mediated osteoimmune signaling involving nuclear factor kappa B (NF-B), tumor necrosis factor alpha (TNF-), sclerostin (SOST) regulatory pathways which provides mechanistic insights into osteopathology. Moreover, in vivo studies were conducted to elucidate experimental challenge models using both oral and intraperitoneal challenge with S. aureus. Findings revealed characteristic BCO lesions, disrupted bone mineralization, and increases trabecular parameters, confirmed with dual-energy X-ray absorptiometry (DEXA), micro-computed tomography (micro-CT), dynamic histomorphometry. Co-challenge with Eimeria spp. revealed intestinal barrier dysfunction and systemic endotoxemia represented by elevated plasma LPS concentrations. These findings were accompanied by gut microbiome changes and altered functional pathways related to inflammation and bone metabolism, providing the evidence on gut-bone axis in BCO pathogenesis. Additionally, dietary supplementation of curcumin demonstrated a positive role in mitigating S. aureus induced BCO reflected as improved bone microarchitecture, decreased bacterial colonization, and modulating systemic inflammatory responses besides preserving growth performance. The findings presented in this thesis establish reproducible experimental models for BCO, decipher the molecular and pathophysiological mechanisms, and mitigation strategy like dietary curcumin for alleviating BCO-associated lameness. These results contribute to the advancement of integrative approach for maintain skeletal integrity and welfare in commercial broiler production.