title: Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis.
abstract: BACKGROUND
  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.
authors.forename: Clémence
authors.initials: C
authors.lastname: Desjardin
authors.forename: Julie
authors.initials: J
authors.lastname: Riviere
authors.forename: Anne
authors.initials: A
authors.lastname: Vaiman
authors.forename: Caroline
authors.initials: C
authors.lastname: Morgenthaler
authors.forename: Mathieu
authors.initials: M
authors.lastname: Diribarne
authors.forename: Michel
authors.initials: M
authors.lastname: Zivy
authors.forename: Céline
authors.initials: C
authors.lastname: Robert
authors.forename: Laurence
authors.initials: L
authors.lastname: Le Moyec
authors.forename: Laurence
authors.initials: L
authors.lastname: Wimel
authors.forename: Olivier
authors.initials: O
authors.lastname: Lepage
authors.forename: Claire
authors.initials: C
authors.lastname: Jacques
authors.forename: Edmond
authors.initials: E
authors.lastname: Cribiu
authors.affiliation: INRA, UMR1313, Biologie Intégrative et Génétique Animale, Jouy-en-Josas, France. laurent.schibler@unceia.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schibler
mesh_terms: D000818:Animals; D006132:Growth Plate / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006734:Horse Diseases / Q000378:metabolism / Q000473:pathology*; D006736:Horses; D007596:Joints / Q000473:pathology; D053858:Metabolic Networks and Pathways; D055034:Osteochondrosis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D040901:Proteomics; D055114:X-Ray Microtomography