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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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Statistical distinction between OC-free (n = 5) and OC(D)-predisposed (n = 5) bone and cartilage samples. (A)Principal Component Analysis (PCA) of Proteomic Data. The PCA reveals a great heterogeneity between predisposed samples in both cartilage and bone. Furthermore, OCD samples (horses OC1, OC2 and OC4) cluster near healthy samples in bone, in contrast to OC (osteochondral defects) (horses OC3 and OC5). This suggests that OCD may result mainly from a cartilage defect, whereas OC may result from a combined cartilage and bone defect. (B)Hierarchical Clustering (HCL) of Proteomic Data. Differentially expressed spots (97 in cartilage, 126 in bone) between healthy OC-free (n = 5) and predisposed (n = 5) samples collected from OC-affected and OC-free foals were used to perform HCL. A distinction could be made between OC-affected and OC-free foals, as well as OCD and OC (osteochondral defects) in both cartilage and bone. In addition, OCD-affected foals have similar profile to OC-free foals based on their bone proteome, suggesting that this lesion subtype shows only a minor defect in bone.
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Fig4: Statistical distinction between OC-free (n = 5) and OC(D)-predisposed (n = 5) bone and cartilage samples. (A)Principal Component Analysis (PCA) of Proteomic Data. The PCA reveals a great heterogeneity between predisposed samples in both cartilage and bone. Furthermore, OCD samples (horses OC1, OC2 and OC4) cluster near healthy samples in bone, in contrast to OC (osteochondral defects) (horses OC3 and OC5). This suggests that OCD may result mainly from a cartilage defect, whereas OC may result from a combined cartilage and bone defect. (B)Hierarchical Clustering (HCL) of Proteomic Data. Differentially expressed spots (97 in cartilage, 126 in bone) between healthy OC-free (n = 5) and predisposed (n = 5) samples collected from OC-affected and OC-free foals were used to perform HCL. A distinction could be made between OC-affected and OC-free foals, as well as OCD and OC (osteochondral defects) in both cartilage and bone. In addition, OCD-affected foals have similar profile to OC-free foals based on their bone proteome, suggesting that this lesion subtype shows only a minor defect in bone.

Mentions: Principal Component Analysis (PCA) showed an important heterogeneity for cartilage and bone samples, especially for OC(D)-affected foals (Figure 4a). Hierarchical clustering (HCL) was also performed based on differentially expressed spots (Figure 4b). Histology, PCA and HCL corroborated the classification of samples as OCD and OC in both cartilage and bone. Furthermore, OCD-predisposed samples (horses OC1, OC2, and OC4) were clustered near OC-free samples in bone, in contrast to OC-predisposed ones (horses OC3 and OC5).Figure 4


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)

Statistical distinction between OC-free (n = 5) and OC(D)-predisposed (n = 5) bone and cartilage samples. (A)Principal Component Analysis (PCA) of Proteomic Data. The PCA reveals a great heterogeneity between predisposed samples in both cartilage and bone. Furthermore, OCD samples (horses OC1, OC2 and OC4) cluster near healthy samples in bone, in contrast to OC (osteochondral defects) (horses OC3 and OC5). This suggests that OCD may result mainly from a cartilage defect, whereas OC may result from a combined cartilage and bone defect. (B)Hierarchical Clustering (HCL) of Proteomic Data. Differentially expressed spots (97 in cartilage, 126 in bone) between healthy OC-free (n = 5) and predisposed (n = 5) samples collected from OC-affected and OC-free foals were used to perform HCL. A distinction could be made between OC-affected and OC-free foals, as well as OCD and OC (osteochondral defects) in both cartilage and bone. In addition, OCD-affected foals have similar profile to OC-free foals based on their bone proteome, suggesting that this lesion subtype shows only a minor defect in bone.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Statistical distinction between OC-free (n = 5) and OC(D)-predisposed (n = 5) bone and cartilage samples. (A)Principal Component Analysis (PCA) of Proteomic Data. The PCA reveals a great heterogeneity between predisposed samples in both cartilage and bone. Furthermore, OCD samples (horses OC1, OC2 and OC4) cluster near healthy samples in bone, in contrast to OC (osteochondral defects) (horses OC3 and OC5). This suggests that OCD may result mainly from a cartilage defect, whereas OC may result from a combined cartilage and bone defect. (B)Hierarchical Clustering (HCL) of Proteomic Data. Differentially expressed spots (97 in cartilage, 126 in bone) between healthy OC-free (n = 5) and predisposed (n = 5) samples collected from OC-affected and OC-free foals were used to perform HCL. A distinction could be made between OC-affected and OC-free foals, as well as OCD and OC (osteochondral defects) in both cartilage and bone. In addition, OCD-affected foals have similar profile to OC-free foals based on their bone proteome, suggesting that this lesion subtype shows only a minor defect in bone.
Mentions: Principal Component Analysis (PCA) showed an important heterogeneity for cartilage and bone samples, especially for OC(D)-affected foals (Figure 4a). Hierarchical clustering (HCL) was also performed based on differentially expressed spots (Figure 4b). Histology, PCA and HCL corroborated the classification of samples as OCD and OC in both cartilage and bone. Furthermore, OCD-predisposed samples (horses OC1, OC2, and OC4) were clustered near OC-free samples in bone, in contrast to OC-predisposed ones (horses OC3 and OC5).Figure 4

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