Ramser Alison, Greene Elizabeth, Wideman Robert, Dridi Sami
Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA.
Department of Poultry Science, Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA.
Cells. 2021 Nov 15;10(11):3174. doi: 10.3390/cells10113174.
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.
复杂疾病状态,如伴骨髓炎的细菌性软骨坏死(BCO),不仅会导致生理症状,如跛行,还会引发涉及免疫和生长因子反应的复杂全身反应。对于现代肉鸡(肉用型鸡)而言,BCO是一个涉及细菌感染、炎症和骨质磨损且病因不明的动物福利、生产及经济问题。因此,明确BCO中关键的炎症和骨相关因子至关重要。在本研究中,阐明了炎症调节剂、细胞因子和趋化因子在局部骨骼和全身血液中的情况,以及炎性小体和关键成纤维细胞生长因子(FGF)基因。受BCO影响的骨骼中细胞因子白细胞介素-1β(IL-1β)表达增加,而受BCO影响的血液中肿瘤坏死因子α(TNFα)和白细胞介素-12表达上调。趋化因子谱显示,除循环中炎性小体NLRC5上调外,受BCO影响的骨骼和血液中白细胞介素-8(IL-8)表达均增加。关键的FGF受体FGFR1在受BCO影响的骨骼中显著下调。将两种不同的骨细胞类型,人永生化成骨细胞(hFOB)和鸡原代软骨细胞,暴露于受BCO影响的鸡的血浆以及重组TNFα中,会导致细胞活力显著下降。这些结果表明促炎和骨吸收因子的表达及其通过对骨细胞活力的影响对BCO病因的潜在作用。这种独特的特征可用于改进BCO的非侵入性检测,并为治疗提供潜在靶点。