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. 2023 Apr 12;13(1):5947.
doi: 10.1038/s41598-023-33060-y.

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

Jennifer Cook  1 , Elizabeth S Greene  1 , Alison Ramser  1 , Garrett Mullenix  1 , Jalila S Dridi  2 , Rohana Liyanage  1 , Robert Wideman  1 , Sami Dridi  3
Affiliations

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

Jennifer Cook et al. Sci Rep. .

Abstract

Bacterial Chondronecrosis with Osteomyelitis (BCO) is a specific cause of lameness in commercial fast-growing broiler (meat-type) chickens and represents significant economic, health, and wellbeing burdens. However, the molecular mechanisms underlying the pathogenesis remain poorly understood. This study represents the first comprehensive characterization of the proximal tibia proteome from healthy and BCO chickens. Among a total of 547 proteins identified, 222 were differentially expressed (DE) with 158 up- and 64 down-regulated proteins in tibia of BCO vs. normal chickens. Biological function analysis using Ingenuity Pathways showed that the DE proteins were associated with a variety of diseases including cell death, organismal injury, skeletal and muscular disorder, immunological and inflammatory diseases. Canonical pathway and protein-protein interaction network analysis indicated that these DE proteins were involved in stress response, unfolded protein response, ribosomal protein dysfunction, and actin cytoskeleton signaling. Further, we identified proteins involved in bone resorption (osteoclast-stimulating factor 1, OSFT1) and bone structural integrity (collagen alpha-2 (I) chain, COL2A1), as potential key proteins involved in bone attrition. These results provide new insights by identifying key protein candidates involved in BCO and will have significant impact in understanding BCO pathogenesis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Stages of proximal femoral degeneration (A–D) and proximal tibial degeneration (E–H) leading progressively to bacterial chondronecrosis with osteomyelitis: (A) Normal proximal femur with white cap of epiphyseal cartilage (e); (B) Femoral head separation (FHS: epiphyseolysis) with the epiphysis remaining in the socket when the femur was disarticulated, revealing the underlying surface of the growth plate or physis (p) and an early region of necrosis (n); (C) Fracturing of the growth plate (p) revealing a necrotic void (nv) within the metaphysis; (D) Terminal femoral head necrosis in which the femoral epiphysis, physis and most of the metaphysis remained attached to the acetabulum when the diaphysis weakened by widely dispersed necrosis was fractured during disarticulation, revealing copious fibrinonecrotic exudate (fe); (E) Normal proximal tibia showing the epiphysis (e) with a secondary center of ossification (*) and the physis/growth plate (p) fully supported by struts of trabecular bone in the metaphyseal zone (m); (F–H) Bacterial infiltration and sequestrae (s), necrotic voids (nv) and microfractures below the growth plate (arrows) provide macroscopic evidence of bone damage associated with osteomyelitis.
Figure 2
Figure 2
Interconnected proteins and predicted upstream regulators built with IPA program for DE protein data that was determined on BCO-affected tibiae. IPA analysis predicted MYC, PR (PGR), and NRF1 (or NFE2L1) as upstream regulators, which were assigned as inhibited or activated according to Z-score. ACTN4, α-actinin 4; ANXA5, annexin A5; APEX1, Apurinic/Apyrimidinic Endodeoxyribonuclease 1; Col2A1; Collagen Type II Alpha 1 Chain ; GCLM; Glutamate-Cysteine Ligase Modifier Subunit ; GLS; Glutaminase; HMOX1; Heme Oxygenase 1; HNRNPA1; Heterogeneous Nuclear Ribonucleoprotein A1; IPO7; Importin 7; LAMP1; Lysosomal Associated Membrane Protein 1; LUM; Lumican; MYC; Myelocytomatosis Oncogene; NFE2L1; NFE2 Like BZIP Transcription Factor 1; PCNA; Proliferating Cell Nuclear Antigen; PGAM1; Phosphoglycerate Mutase 1; PGR (PR); progesterone receptor; PKM; Pyruvate Kinase M1/2; PLS3; plastin 3; PSMA; Proteasome 20S Subunit Alpha 6; PSMD; Proteasome 26S Subunit, Non-ATPase 1; RPL; Ribosomal Protein L6; RPS; ribosomal protein S3A1; STAT; Signal Transducer And Activator Of Transcription; TF; Transferrin; VDAC2, voltage-dependent anion channel 2.
Figure 3
Figure 3
Validation of selected protein-encoding genes. Protein expression was determined by Western blot (a, b) and mRNA abundances were measured by qPCR and 2-ΔΔCT method. Data are mean ± SEM and * indicates a significant difference at P < 0.05. ACLY, ATP citrate lyase; ACTB, β actin; ACTN4, α-actinin 4; Col2A1, Collagen Type II Alpha 1 Chain; HSP90, heat shock protein 90; MYC, myelocytomatosis oncogene; NCAM1, Neural Cell Adhesion Molecule 1; NRF1/2, erythroid 2-related factor 1/2; OSTF1, Osteoclast-stimulating factor-1; STAT3, Signal Transducer And Activator Of Transcription 3; VCL, vinculin.
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