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Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis.

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 - BMC Genomics (2014)

Bottom Line: 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.Consequently, results are not confounded by changes associated with the evolution of the lesion, but focus on altered constitutive molecular mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313, Biologie Intégrative et Génétique Animale, Jouy-en-Josas, France. laurent.schibler@unceia.fr.

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).

Conclusion: 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.

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Related in: MedlinePlus

Investigation of type-VI collagen localization and chondrocyte organization. Upper Panel - Type-VI collagen localization by immunostaining. Both lesion types (OCD [f] and osteochondral defects (OC) [s]) were characterized by positively stained areas (arrows) indicative of cartilage dedifferentiation leading to the formation of local scar tissue (fibrocartilage). Lower Panel - Magnification views (x20) of animals OC1-OC4 showing chondrocyte clusters located surrounding (s) or close to the lesions (c), which may reflect a healing process is underway.
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Fig3: Investigation of type-VI collagen localization and chondrocyte organization. Upper Panel - Type-VI collagen localization by immunostaining. Both lesion types (OCD [f] and osteochondral defects (OC) [s]) were characterized by positively stained areas (arrows) indicative of cartilage dedifferentiation leading to the formation of local scar tissue (fibrocartilage). Lower Panel - Magnification views (x20) of animals OC1-OC4 showing chondrocyte clusters located surrounding (s) or close to the lesions (c), which may reflect a healing process is underway.

Mentions: Type-I collagen immunostaining revealed large areas of chondrocyte dedifferentiation in the lesion. In addition, type-VI collagen was widely distributed in the lesion (upper panel Figure 3), contrasting with the usual localization at the pericellular region (chondron) in OC-free articular cartilage. Chondrocyte dedifferentiation and type-VI collagen expression are suggestive of fibrocartilage. Abnormal chondrocyte clusters were observed at different localizations: surrounding the lesions, close to the lesions, and distant from the lesions in horses OC1-OC4 (lower panel Figure 3). Based on histology, OC lesions were classified into two groups: 1) osteochondral defects with invagination of articular cartilage, progressive dedifferentiation and high type-VI collagen expression (horses OC3 and OC4); and 2) lesions with major cartilage loss (horse OC5), with low type-VI collagen expression.Figure 3


Omics technologies provide new insights into the molecular physiopathology of equine osteochondrosis.

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 - BMC Genomics (2014)

Investigation of type-VI collagen localization and chondrocyte organization. Upper Panel - Type-VI collagen localization by immunostaining. Both lesion types (OCD [f] and osteochondral defects (OC) [s]) were characterized by positively stained areas (arrows) indicative of cartilage dedifferentiation leading to the formation of local scar tissue (fibrocartilage). Lower Panel - Magnification views (x20) of animals OC1-OC4 showing chondrocyte clusters located surrounding (s) or close to the lesions (c), which may reflect a healing process is underway.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4233069&req=5

Fig3: Investigation of type-VI collagen localization and chondrocyte organization. Upper Panel - Type-VI collagen localization by immunostaining. Both lesion types (OCD [f] and osteochondral defects (OC) [s]) were characterized by positively stained areas (arrows) indicative of cartilage dedifferentiation leading to the formation of local scar tissue (fibrocartilage). Lower Panel - Magnification views (x20) of animals OC1-OC4 showing chondrocyte clusters located surrounding (s) or close to the lesions (c), which may reflect a healing process is underway.
Mentions: Type-I collagen immunostaining revealed large areas of chondrocyte dedifferentiation in the lesion. In addition, type-VI collagen was widely distributed in the lesion (upper panel Figure 3), contrasting with the usual localization at the pericellular region (chondron) in OC-free articular cartilage. Chondrocyte dedifferentiation and type-VI collagen expression are suggestive of fibrocartilage. Abnormal chondrocyte clusters were observed at different localizations: surrounding the lesions, close to the lesions, and distant from the lesions in horses OC1-OC4 (lower panel Figure 3). Based on histology, OC lesions were classified into two groups: 1) osteochondral defects with invagination of articular cartilage, progressive dedifferentiation and high type-VI collagen expression (horses OC3 and OC4); and 2) lesions with major cartilage loss (horse OC5), with low type-VI collagen expression.Figure 3

Bottom Line: 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.Consequently, results are not confounded by changes associated with the evolution of the lesion, but focus on altered constitutive molecular mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313, Biologie Intégrative et Génétique Animale, Jouy-en-Josas, France. laurent.schibler@unceia.fr.

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).

Conclusion: 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.

Show MeSH
Related in: MedlinePlus