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  1. Article: Characterisation of key proteoglycans in the cranial cruciate ligaments (CCLs) from two dog breeds with different predispositions to CCL disease and rupture

    Allaith, S / Tew, S.R / Hughes, C.E / Clegg, P.D / Canty-Laird, E.G / Comerford, E.J

    veterinary journal. 2021 June, v. 272

    2021  

    Abstract: Cranial cruciate ligament disease and rupture (CCLD/R) is one of the most common orthopaedic conditions in dogs, eventually leading to osteoarthritis of the stifle joint. Certain dog breeds such as the Staffordshire bull terrier have an increased risk of ...

    Abstract Cranial cruciate ligament disease and rupture (CCLD/R) is one of the most common orthopaedic conditions in dogs, eventually leading to osteoarthritis of the stifle joint. Certain dog breeds such as the Staffordshire bull terrier have an increased risk of developing CCLD/R. Previous studies into CCLD/R have found that glycosaminoglycan levels were elevated in cranial cruciate ligament (CCL) tissue from high-risk breeds when compared to the CCL from a low-risk breed to CCLD/R. Our objective was to determine specific proteoglycans/glycosaminoglycans in the CCL and to see whether their content was altered in dog breeds with differing predispositions to CCLD/R. Disease-free CCLs from Staffordshire bull terriers (moderate/high-risk to CCLD/R) and Greyhounds (low-risk to CCLD/R) were collected and key proteoglycan/glycosaminoglycans were determined by semi-quantitative Western blotting, quantitative biochemistry, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry.Gene expression of fibromodulin (P = 0.03), aggrecan (P = 0.0003), and chondroitin-6-sulphate stubs (P = 0.01) were significantly increased, and for fibromodulin this correlated with an increase in protein content in Staffordshire bull terriers compared to Greyhound CCLs (P = 0.02). Decorin (P = 0.03) and ADAMTS-4 (P = 0.04) gene expression were significantly increased in Greyhounds compared to Staffordshire bull terrier CCLs. The increase of specific proteoglycans and glycosaminoglycans within the Staffordshire bull terrier CCLs may indicate a response to higher compressive loads, potentially altering their risk to traumatic injury. The higher decorin content in the Greyhound CCLs is essential for maintaining collagen fibril strength, while the increase of ADAMTS-4 indicates a higher rate of turnover helping to regulate normal CCL homeostasis in Greyhounds.
    Keywords Bull Terrier ; Greyhound ; collagen ; cranial cruciate ligament ; dogs ; gene expression ; glycosaminoglycans ; homeostasis ; orthopedics ; osteoarthritis ; protein content ; proteoglycans ; reverse transcriptase polymerase chain reaction ; risk ; stifle
    Language English
    Dates of publication 2021-06
    Publishing place Elsevier Ltd
    Document type Article
    Note NAL-light
    ZDB-ID 428614-5
    ISSN 1532-2971 ; 0372-5545 ; 1090-0233
    ISSN (online) 1532-2971
    ISSN 0372-5545 ; 1090-0233
    DOI 10.1016/j.tvjl.2021.105657
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: Characterisation of key proteoglycans in the cranial cruciate ligaments (CCLs) from two dog breeds with different predispositions to CCL disease and rupture.

    Allaith, S / Tew, S R / Hughes, C E / Clegg, P D / Canty-Laird, E G / Comerford, E J

    Veterinary journal (London, England : 1997)

    2021  Volume 272, Page(s) 105657

    Abstract: Cranial cruciate ligament disease and rupture (CCLD/R) is one of the most common orthopaedic conditions in dogs, eventually leading to osteoarthritis of the stifle joint. Certain dog breeds such as the Staffordshire bull terrier have an increased risk of ...

    Abstract Cranial cruciate ligament disease and rupture (CCLD/R) is one of the most common orthopaedic conditions in dogs, eventually leading to osteoarthritis of the stifle joint. Certain dog breeds such as the Staffordshire bull terrier have an increased risk of developing CCLD/R. Previous studies into CCLD/R have found that glycosaminoglycan levels were elevated in cranial cruciate ligament (CCL) tissue from high-risk breeds when compared to the CCL from a low-risk breed to CCLD/R. Our objective was to determine specific proteoglycans/glycosaminoglycans in the CCL and to see whether their content was altered in dog breeds with differing predispositions to CCLD/R. Disease-free CCLs from Staffordshire bull terriers (moderate/high-risk to CCLD/R) and Greyhounds (low-risk to CCLD/R) were collected and key proteoglycan/glycosaminoglycans were determined by semi-quantitative Western blotting, quantitative biochemistry, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry. Gene expression of fibromodulin (P = 0.03), aggrecan (P = 0.0003), and chondroitin-6-sulphate stubs (P = 0.01) were significantly increased, and for fibromodulin this correlated with an increase in protein content in Staffordshire bull terriers compared to Greyhound CCLs (P = 0.02). Decorin (P = 0.03) and ADAMTS-4 (P = 0.04) gene expression were significantly increased in Greyhounds compared to Staffordshire bull terrier CCLs. The increase of specific proteoglycans and glycosaminoglycans within the Staffordshire bull terrier CCLs may indicate a response to higher compressive loads, potentially altering their risk to traumatic injury. The higher decorin content in the Greyhound CCLs is essential for maintaining collagen fibril strength, while the increase of ADAMTS-4 indicates a higher rate of turnover helping to regulate normal CCL homeostasis in Greyhounds.
    MeSH term(s) ADAMTS4 Protein/analysis ; ADAMTS4 Protein/genetics ; Aggrecans/analysis ; Aggrecans/genetics ; Animals ; Anterior Cruciate Ligament/chemistry ; Chondroitin Sulfates/analysis ; Chondroitin Sulfates/genetics ; Dog Diseases/genetics ; Dogs ; Fibromodulin/analysis ; Fibromodulin/genetics ; Gene Expression ; Genetic Predisposition to Disease/genetics ; Joint Diseases/genetics ; Joint Diseases/veterinary ; Proteoglycans/analysis ; Proteoglycans/genetics ; Rupture, Spontaneous/genetics ; Rupture, Spontaneous/veterinary ; Species Specificity ; Stifle
    Chemical Substances Aggrecans ; Proteoglycans ; Fibromodulin (126468-95-9) ; Chondroitin Sulfates (9007-28-7) ; ADAMTS4 Protein (EC 3.4.24.82)
    Language English
    Publishing date 2021-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 428614-5
    ISSN 1532-2971 ; 0372-5545 ; 1090-0233
    ISSN (online) 1532-2971
    ISSN 0372-5545 ; 1090-0233
    DOI 10.1016/j.tvjl.2021.105657
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Variations during ageing in the three-dimensional anatomical arrangement of fascicles within the equine superficial digital flexor tendon.

    Ali, O J / Comerford, E J / Clegg, P D / Canty-Laird, E G

    European cells & materials

    2018  Volume 35, Page(s) 87–102

    Abstract: BiTendons are constructed from collagenous fascicles separated by endotenon/interfascicular matrix (IFM). Tendons may be specialised for precision movement or to store energy during locomotion and for the latter the elasticity of the endotenon/IFM is ... ...

    Abstract BiTendons are constructed from collagenous fascicles separated by endotenon/interfascicular matrix (IFM). Tendons may be specialised for precision movement or to store energy during locomotion and for the latter the elasticity of the endotenon/IFM is particularly important. The equine superficial digital flexor tendon (SDFT) is a dedicated energy-storing tendon with a similar function to the human Achilles tendon. Classical anatomical descriptions portray fascicles as longitudinally arranged distinct anatomical structures. In the present study, using three-dimensional reconstruction from whole tissue slices and histological sections, the fascicles of the equine SDFT were found to adopt a complex interweaved arrangement. Fascicles were found to fully and partially converge and diverge within the tendon and fascicle bundles were observed. Fascicle morphology was not homogenous with narrowing, broadening and twisted fascicles observed in addition to relatively straight fascicles. The number of fascicle bundles observed in cross-section increased from the proximal to the distal end of the tendon, whilst the number of fascicles decreased with age in the proximal region. Fascicular patterns were not similar between the left and right limbs, across different regions or at different ages. A decrease in thickness of the endotenon/IFM between fascicles with age was found in the distal tendon region. The results provide a rationale for considering fascicular organisation when diagnosing and treating tendon injuries, for bioengineering tendon and when modelling tendon function.
    MeSH term(s) Aging/physiology ; Animals ; Body Patterning ; Embryonic Development ; Fetus/anatomy & histology ; Horses/embryology ; Horses/physiology ; Imaging, Three-Dimensional ; Tendons/anatomy & histology ; Tendons/embryology
    Language English
    Publishing date 2018-02-13
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2046669-9
    ISSN 1473-2262 ; 1473-2262
    ISSN (online) 1473-2262
    ISSN 1473-2262
    DOI 10.22203/eCM.v035a07
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Insulin-like growth factor binding protein (IGFBP6) is a cross-species tendon marker.

    Turlo, A J / Mueller-Breckenridge, A J / Zamboulis, D E / Tew, S R / Canty-Laird, E G / Clegg, P D

    European cells & materials

    2019  Volume 38, Page(s) 123–136

    Abstract: The main challenge in tendon injury management is suboptimal tissue healing that fails to re-establish original tendon function. Tissue bioengineering is a promising approach for tendon therapy, with potential to improve its functional outcomes. However, ...

    Abstract The main challenge in tendon injury management is suboptimal tissue healing that fails to re-establish original tendon function. Tissue bioengineering is a promising approach for tendon therapy, with potential to improve its functional outcomes. However, evaluation criteria for tissue-engineered tendon are unclear due to the lack of specific markers of differentiated tendon. The study aim was to identify a panel of genes that characterised tendons in comparison to cartilage or muscles and validate those genes, both in human and key species used as models for tendon diseases. Gene expression profiling of rat tendon and cartilage in whole-tissue samples and primary tenocytes and chondrocytes was undertaken using two independent microarray platforms. Genes that demonstrated high expression correlation across two assays were validated by qRT-PCR in rat tendon relative to cartilage and muscle. Five genes demonstrating the highest tendon-related expression in the validation experiment (ASPN, ECM1, IGFBP6, TNMD, THBS4) were further evaluated by qRT-PCR in ovine, equine and human tissue. The group of tendon markers, identified by unbiased transcriptomic analysis of rat musculoskeletal tissues, demonstrated species-dependent profiles of expression. Insulin-like growth factor binding protein 6 (IGFBP6) was identified as the only universal tendon marker. Further investigation in equine tendon showed that IGFBP6 expression was not affected by ageing or tendon function but decreased in anatomical regions subjected to elevated compressive force. IGFBP6 is a robust cross-species marker of tendon phenotype and may find application in evaluation of tendon physiology and guided differentiation of permissive cells towards functional tenocytes.
    MeSH term(s) Animals ; Biomarkers/metabolism ; Cells, Cultured ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/metabolism ; Horses ; Humans ; Insulin-Like Growth Factor Binding Protein 6/genetics ; Insulin-Like Growth Factor Binding Protein 6/metabolism ; Rats ; Sheep ; Species Specificity ; Tendons/metabolism ; Tenocytes/metabolism ; Tissue Engineering/methods ; Transcriptome
    Chemical Substances Biomarkers ; Extracellular Matrix Proteins ; Insulin-Like Growth Factor Binding Protein 6
    Language English
    Publishing date 2019-09-24
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2046669-9
    ISSN 1473-2262 ; 1473-2262
    ISSN (online) 1473-2262
    ISSN 1473-2262
    DOI 10.22203/eCM.v038a10
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A systems biology approach to defining regulatory mechanisms for cartilage and tendon cell phenotypes.

    Mueller, A J / Tew, S R / Vasieva, O / Clegg, P D / Canty-Laird, E G

    Scientific reports

    2016  Volume 6, Page(s) 33956

    Abstract: Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and ... ...

    Abstract Phenotypic plasticity of adult somatic cells has provided emerging avenues for the development of regenerative therapeutics. In musculoskeletal biology the mechanistic regulatory networks of genes governing the phenotypic plasticity of cartilage and tendon cells has not been considered systematically. Additionally, a lack of strategies to effectively reproduce in vitro functional models of cartilage and tendon is retarding progress in this field. De- and redifferentiation represent phenotypic transitions that may contribute to loss of function in ageing musculoskeletal tissues. Applying a systems biology network analysis approach to global gene expression profiles derived from common in vitro culture systems (monolayer and three-dimensional cultures) this study demonstrates common regulatory mechanisms governing de- and redifferentiation transitions in cartilage and tendon cells. Furthermore, evidence of convergence of gene expression profiles during monolayer expansion of cartilage and tendon cells, and the expression of key developmental markers, challenges the physiological relevance of this culture system. The study also suggests that oxidative stress and PI3K signalling pathways are key modulators of in vitro phenotypes for cells of musculoskeletal origin.
    Language English
    Publishing date 2016-09-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep33956
    Database MEDical Literature Analysis and Retrieval System OnLINE

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