Comprehensive Analyses of Bone and Cartilage Transcriptomes Evince Ion Transport, Inflammation and Cartilage Development-Related Genes Involved in Chickens’ Femoral Head Separation

SIMPLE SUMMARY: Femoral head necrosis (FHN) and other locomotor problems cause severe impacts on the poultry industry due to huge economic losses and reduced animal welfare. Femoral head separation (FHS), the initial phase of FHN, is usually a subclinical condition characterized by the detachment of articular cartilage from the bone. In this study, we aimed to identify genes and biological processes involved with FHS in broilers. A better understanding of the FHS molecular mechanisms can help to develop strategies to reduce this condition in chickens. Here, we described several genes that have their expression altered in the articular cartilage and femur when normal and FHS-affected animals were compared. Furthermore, genetic variants were found differing between the studied groups. Therefore, performing an integrated analysis of these datasets, we were able to detect genes and variants related to FHS in chickens. Some of them, such as SLC4A1, RHAG, ANK1, MKNK2, SPTB, ADA, C7 and EPB420 genes were highlighted and should be further explored to validate them as candidates to FHS and FHN in chickens and possibly in humans. ABSTRACT: Femoral head separation (FHS) is usually a subclinical condition characterized by the detachment of articular cartilage from the bone. In this study, a comprehensive analysis identifying shared and exclusive expression profiles, biological processes (BP) and variants related to FHS in the femoral articular cartilage and growth plate in chickens was performed through RNA sequencing analysis. Thirty-six differentially expressed (DE) genes were shared between femoral articular cartilage (AC) and growth plate (GP) tissues. Out of those, 23 genes were enriched in BP related to ion transport, translation factors and immune response. Seventy genes were DE exclusively in the AC and 288 in the GP. Among the BP of AC, the response against bacteria can be highlighted, and for the GP tissue, the processes related to chondrocyte differentiation and cartilage development stand out. When the chicken DE genes were compared to other datasets, eight genes (SLC4A1, RHAG, ANK1, MKNK2, SPTB, ADA, C7 and EPB420) were shared between chickens and humans. Furthermore, 89 variants, including missense in the SPATS2L, PRKAB1 and TRIM25 genes, were identified between groups. Therefore, those genes should be more explored to validate them as candidates to FHS/FHN in chickens and humans.