Local and Systemic Cytokine, Chemokine, and FGF Profile in Bacterial Chondronecrosis with Osteomyelitis (BCO)-Affected Broilers

Abstract

Complex disease states, like bacterial chondronecrosis with osteomyelitis (BCO), not only result in physiological symptoms, such as lameness, but also a complex systemic reaction involving immune and growth factor responses. For the modern broiler (meat-type) chickens, BCO is an animal welfare, production, and economic concern involving bacterial infection, inflammation, and bone attrition with a poorly defined etiology. It is, therefore, critical to define the key inflammatory and bone-related factors involved in BCO. In this study, the local bone and systemic blood profile of inflammatory modulators, cytokines, and chemokines was elucidated along with inflammasome and key FGF genes. BCO-affected bone showed increased expression of cytokines IL-1β, while BCO-affected blood expressed upregulated TNFα and IL-12. The chemokine profile revealed increased IL-8 expression in both BCO-affected bone and blood in addition to inflammasome NLRC5 being upregulated in circulation. The key FGF receptor, FGFR1, was significantly downregulated in BCO-affected bone. The exposure of two different bone cell types, hFOB and chicken primary chondrocytes, to plasma from BCO-affected birds, as well as recombinant TNFα, resulted in significantly decreased cell viability. These results demonstrate an expression of proinflammatory and bone-resorptive factors and their potential contribution to BCO etiology through their impact on bone cell viability. This unique profile could be used for improved non-invasive detection of BCO and provides potential targets for treatments.

Comparative- and network-based proteomic analysis of bacterial chondronecrosis with osteomyelitis lesions in broiler’s proximal tibiae identifies new molecular signatures of lameness

“…Moreover, infection of human endothelial (HUVEC) cells with Staphylococcus aureus (also the leading cause of BCO) 3 has been shown to induce proteasome subunits at 16 h post-infection 33 , 34 . Immune and pro-inflammatory pathways have been found to be dependent on both proteasomal activity and ubiquitylation 35 , and our previous studies have shown that pro-inflammatory cytokines, such as IL-1β and TNFα, were induced in BCO-affected chickens at local and systemic levels 36 . This proteasome-induced inflammation is probably mediated through NF-κB and MAPK pathways that merit future investigations 37 .…”

Downregulation of growth plate genes involved with the onset of femoral head separation in young broilers

“…FHS is characterized by the detachment of GP and AC, occurring in tibia and femur (Durairaj et al, 2009;Packialakshmi et al, 2015). Although some studies have been published in the last years with FHS, FHN, and BCO, including by our group, there are few of them approaching the molecular mechanisms involved with these conditions, especially with early ages (Li et al, 2015;Paludo et al, 2017;Peixoto et al, 2019;Oliveira et al, 2020;Liu K. et al, 2021;Hul et al, 2021;Ramser et al, 2021Ramser et al, , 2022Goldoni et al, 2022;Santos et al, 2022). To the best of our knowledge, this paper is the first attempt to compare normal and FHS-affected femoral head transcriptome in broilers with 21 days of age.…”

“…Some authors classified FHN depending on its severity, such as femoral head separation (FHS), when the growth plate is separated from cartilage and femoral head separation with growth plate lacerations (FHSL), when there are lesions in the femoral growth plate ( Li et al, 2015 ; Packialakshmi et al, 2015 ). This condition is also known as bacterial chondronecrosis with osteomyelitis (BCO) when it is associated with bacterial infection ( Jiang et al, 2015 ; Al-rubaye et al, 2017 ; Ramser et al, 2021 ).…”

“… Oliveira et al (2020) also pointed out that osteochondral downregulated genes are potentially triggering BCO in tibia of 42-day-old broilers. Most of the studies with FHN/FHS in chickens are focused on understanding the ossification processes and, generally, in animals older than 35 days of age ( Li et al, 2015 ; Paludo et al, 2017 ; Peixoto et al, 2019 ; Hul et al, 2021 ; Ramser et al, 2021 , 2022 ), since the highest incidences of this condition occur at these ages ( McNamee and Smyth, 2000 ; Paxton et al, 2014 ; Packialakshmi et al, 2015 ). Therefore, molecular mechanisms involved with femoral head separation in young age (21 days) broilers were identified using RNA sequencing, allowing highlighting genes and BP potentially related to the onset of this condition.…”

Bone Metabolite Profile Differs between Normal and Femur Head Necrosis (FHN/BCO)-Affected Broilers: Implications for Dysregulated Metabolic Cascades in FHN Pathophysiology

“…Finally, the exact progression and mechanism by which FHN develops in broilers has yet to be elucidated, making non-invasive means of detection, such as circulating biomarkers, yet to be found. However, a recent study found differentially expressed cytokine and chemokine profiles in the local bone and blood of FHN-affected broilers compared to normal, healthy broilers [ 10 ]. Other researchers have utilized high-throughput transcriptomics and proteomics and identified key cartilage and bone growth as well as lipid metabolism and immune-related factors in FHS and FHN [ 11 , 12 ].…”