Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis.
Abstract: Osteochondrosis (OC(D)) is a juvenile osteo-articular disorder affecting several mammalian species. In horses, OC(D) is considered as a multifactorial disease and has been described as a focal disruption of endochondral ossification leading to the development of osteoarticular lesions. Nevertheless, OC(D) physiopathology is poorly understood. Affected horses may present joint swelling, stiffness and lameness. Thus, OC(D) is a major concern for the equine industry. Our study was designed as an integrative approach using omics technologies for the identification of constitutive defects in epiphyseal cartilage and/or subchondral bone associated with the development of primary lesions to further understand OC(D) pathology. This study compared samples from non-affected joints (hence lesion-free) from OC(D)-affected foals (n = 5, considered predisposed samples) with samples from OC-free foals (n = 5) considered as control samples. Consequently, results are not confounded by changes associated with the evolution of the lesion, but focus on altered constitutive molecular mechanisms. Comparative proteomics and micro computed tomography analyses were performed on predisposed and OC-free bone and cartilage samples. Metabolomics was also performed on synovial fluid from OC-free, OC(D)-affected and predisposed joints. Results: Two lesion subtypes were identified: OCD (lesion with fragment) and OC (osteochondral defects). Modulated proteins were identified using omics technologies (2-DE proteomics) in cartilage and bone from affected foals compare to OC-free foals. These were associated with cellular processes including cell cycle, energy production, cell signaling and adhesion as well as tissue-specific processes such as chondrocyte maturation, extracellular matrix and mineral metabolism. Of these, five had already been identified in synovial fluid of OC-affected foals: ACTG1 (actin, gamma 1), albumin, haptoglobin, FBG (fibrinogen beta chain) and C4BPA (complement component 4 binding protein, alpha). Conclusions: This study suggests that OCD lesions may result from a cartilage defect whereas OC lesions may be triggered by both bone and cartilage defects, suggesting that different molecular mechanisms responsible for the equine osteochondrosis lesion subtypes and predisposition could be due to a defect in both bone and cartilage. This study will contribute to refining the definition of OC(D) lesions and may improve diagnosis and development of therapies for horses and other species, including humans.
Publication Date: 2014-10-31 PubMed ID: 25359417PubMed Central: PMC4233069DOI: 10.1186/1471-2164-15-947Google Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article discusses how the use of omics technologies have increased understanding of equine osteochondrosis. It progresses to explain how these technologies were used to identify altered molecular mechanisms within bone and cartilage that could potentially lead to the development of the disease.
Research Objective
- The study aimed to identify the elements in bone and cartilage that could potentially lead to the onset of equine osteochondrosis (OC(D)), a juvenile osteo-articular disorder that affects horses. The disorder is a significant concern for horse breeders and owners because it can lead to joint stiffness, limb lameness, and swelling.
Methodology
- The study compared the joints of foals displaying OC(D) symptoms with those of foal samples not affected by the disease. To do this, the researchers used omics technologies to study and compare the samples. Omics technologies refer to the different types of biological analysis approaches in genomics, proteomics, metabolomics and others that seek comprehensive and holistic views of the structures, functions, and dynamics of an organism or populations of organisms.
- These comparisons were done in a way that did not factor in changes associated with the evolution of the lesion but focused on altered molecular mechanisms that might have led to the onset of the disease.
- They performed comparative proteomics and micro computed tomography analyses on healthy and predisposed bone and cartilage samples. They also performed metabolomics on synovial fluid, which is a viscous liquid found in small quantities in the cavities of the synovial joints.
Results
- Through their research, the team turned up two OC(D) subtypes: Osteochondrosis dissecans (OCD) – which left a lesion with fragment- and osteochondral defects (OC), through the use of omics technologies they were also able to identify proteins that were modulated in cartilage and bone samples from foals affected by OC(D) in comparison to samples not affected by the disease.
- They established that the modulated proteins were associated with cellular processes including energy production, cell signalling, cell cycle, tissue-specific processes such as mineral metabolism, extracellular matrix and chondrocyte maturation.
- Furthermore, five of these proteins, which included fibrinogen beta chain (FBG), albumin, actin, gamma 1 (ACTG1), complement component 4 binding protein, alpha (C4BPA), and haptoglobin, had already been identified in synovial fluid of OC(D)-affected foals.
Conclusions
- The study suggested that OC(D) lesions likely result from a defect in cartilage or bone, and that different molecular mechanisms could be responsible for the specific types of equine osteochondrosis lesions found.
- The researchers believe this study will help improve the definition of OC(D) lesions and potentially contribute to the development of therapeutic solutions to treat the disorder in horses and possibly even humans.
Cite This Article
APA
Desjardin C, Riviere J, Vaiman A, Morgenthaler C, Diribarne M, Zivy M, Robert C, Le Moyec L, Wimel L, Lepage O, Jacques C, Cribiu E, Schibler L.
(2014).
Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis.
BMC Genomics, 15(1), 947.
https://doi.org/10.1186/1471-2164-15-947 Publication
Researcher Affiliations
- INRA, UMR1313, Biologie Intégrative et Génétique Animale, Jouy-en-Josas, France. laurent.schibler@unceia.fr.
MeSH Terms
- Animals
- Growth Plate / diagnostic imaging
- Growth Plate / metabolism
- Growth Plate / pathology
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Joints / pathology
- Metabolic Networks and Pathways
- Osteochondrosis / metabolism
- Osteochondrosis / pathology
- Osteochondrosis / veterinary
- Proteomics
- X-Ray Microtomography
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Citations
This article has been cited 3 times.- Tran H, McConville M, Loukopoulos P. Metabolomics in the study of spontaneous animal diseases. J Vet Diagn Invest 2020 Sep;32(5):635-647.
- Chiaradia E, Pepe M, Orvietani PL, Renzone G, Magini A, Sforna M, Emiliani C, Di Meo A, Scaloni A. Proteome Alterations in Equine Osteochondrotic Chondrocytes. Int J Mol Sci 2019 Dec 7;20(24).
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