Changes of bone remodeling, cartilage damage and apoptosis-related pathways in broilers with femoral head necrosis 1

Femoral head necrosis (FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage. The mechanism behind abnormal apoptosis in FHN broilers, leading to cartilage damage, remains unclear; although endoplasmic reticulum stress (ERS) has been found to play a role in glucocorticoid-induced FHN broilers. In this study, we collected samples from broilers with femoral head separation (FHS) and femoral head separation accompanied with growth plate lacerations (FHSL) in a broiler farm. The aim was to investigate the potential association between the severity of FHN, bone remodeling and cartilage damage. Additionally, primary chondrocytes were treated with methylprednisolone (MP) to construct an in vitro FHN model, followed by inhibition or activation of ERS or hypoxia inducible factor-1α (HIF-1α) to further investigate the mechanism of apoptosis in cartilage. The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN, as the degree of cartilage damage was found to be closely related to the severity of the disease. Bone quality was only affected in FHSL broilers, although factors related to bone metabolism were significantly altered among FHN-affected broilers. In addition, cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α, which was consistent with both in vivo and in vitro findings after MP treatment. The results were further supported by treatment with HIF-1α or ERS inhibition or activation. In conclusion, bone remodeling and cartilage homeostasis were affected in FHN broilers, but only cartilage damage was significantly exacerbated with FHN development. Moreover, activation of ERS or HIF-1α resulted in apoptosis in cartilage, thus exhibiting a significant correlation with FHN severity.