Dataset Information

Dog as a Model for Osteoarthritis: The FGF4 Retrogene Insertion May Matter.

ABSTRACT: Osteoarthritis (OA) is a degenerative joint disease associated with chronic pain and disability in humans and companion animals. The canine species can be subdivided into non-chondrodystrophic (NCD) and chondrodystrophic (CD) dogs, the latter having disproportionally short limbs due to disturbance in endochondral ossification of long bones. This phenotype is associated with retrogene insertions of the fibroblast growth factor 4 (FGF4) gene, resulting in enhanced fibroblast growth factor receptor 3 (FGFR3) signaling. The effect on cartilage is unknown and in experimental studies with dogs, breeds are seemingly employed randomly. The aim of this study was to determine whether CD- and NCD-derived cartilage differs on a structural and biochemical level, and to explore the relationship between FGF4 associated chondrodystrophy and OA. Cartilage explants from CD and NCD dogs were cultured for 21 days. Activation of canonical Wnt signaling was assessed in primary canine chondrocytes. OA and synovitis severity from an experimental OA model were compared between healthy and OA samples from CD and NCD dogs. Release of glycosaminoglycans, DNA content, and cyclooxygenase 2 (COX-2) expression were higher in NCD cartilage explants. Healthy cartilage from NCD dogs displayed higher cartilage degeneration and synovitis scores, which was aggravated by the induction of OA. Dikkopf-3 gene expression was higher in NCD cartilage. No differences in other Wnt pathway read outs were found. To conclude, chondrodystrophy associated with the FGF4 retrogene seems to render CD dogs less susceptible to the development of OA when compared with NCD dogs. These differences should be considered when choosing a canine model to study the pathobiology and new treatment strategies of OA. © 2019 The Authors. Journal of Orthopaedic Research^® Published by Wiley Periodicals, Inc. J Orthop Res 37:2550-2560, 2019.

SUBMITTER: Tellegen AR

PROVIDER: S-EPMC6899624 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Dog as a Model for Osteoarthritis: The FGF4 Retrogene Insertion May Matter.

Tellegen Anna R AR Dessing Aileen J AJ Houben Kaat K Riemers Frank M FM Creemers Laura B LB Mastbergen Simon C SC Meij Björn P BP Miranda-Bedate Alberto A Tryfonidou Marianna A MA

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20190813 12

Osteoarthritis (OA) is a degenerative joint disease associated with chronic pain and disability in humans and companion animals. The canine species can be subdivided into non-chondrodystrophic (NCD) and chondrodystrophic (CD) dogs, the latter having disproportionally short limbs due to disturbance in endochondral ossification of long bones. This phenotype is associated with retrogene insertions of the fibroblast growth factor 4 (FGF4) gene, resulting in enhanced fibroblast growth factor receptor ...[more]

PMID: 31373395

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Project description:Canine osteoarthritis is a common, painful condition that is typically managed in a general practice setting. Osteoarthritis may have significant negative impacts on the welfare of both dogs and their owners. Anticipated early clinical signs of canine osteoarthritis and the preferred route to its diagnosis are well described by veterinary subject experts in published literature. However, little is known about changes owners first recognise in a dog ultimately diagnosed with osteoarthritis, how they make decisions about when to present that dog to a general practitioner, or whether the described diagnostic pathways are followed by general practitioners. The aim of this research was to investigate how dog owners and veterinary surgeons describe identifying and diagnosing canine osteoarthritis. Owners of osteoarthritic dogs were recruited for semi-structured interview, and veterinary surgeons working in general practice were invited to take part in practice-based focus groups. Transcripts from both datasets were thematically analysed using a contextualist epistemology with an ontology based on critical realism to construct convergent themes from latent and semantic codes. Thirty-two interviews were completed with 40 owners from 32 households who discussed 35 dogs with osteoarthritis, and 26 veterinary surgeons engaged in four practice-based focus groups. Owners described identifying a wide range of acute and chronic, typically subtle and intermittent, behavioural and demeanour changes prior to their dogs' osteoarthritis diagnosis. Few attributed these changes to canine osteoarthritis, and some waited many months before presenting their dog to a veterinary practice. Veterinary surgeons described a consistent 'typical osteoarthritis' presentation that they recognised through history taking and clinical examination. Their diagnostic work-up rarely followed that advocated by subject experts for reasons including lack of time and perceptions that it would not change the outcome. Many veterinary surgeons described frustration that some owners did not accept their recommendations to provide analgesia for affected dogs. Short consultation lengths, poor awareness of owner knowledge levels, and lack of recognition of the importance of owners' prior knowledge, beliefs and assumptions may contribute to these consultations being perceived as challenging by some veterinary surgeons and owners. This research demonstrates that veterinary surgeons and owners want dogs with clinical signs of osteoarthritis to be happy and comfortable, but that ineffective communication and lack of trust in the consulting room may be a barrier. Our data identifies many new avenues for future research and improved communication strategies that could facilitate earlier identification and treatment of canine osteoarthritis in general practice.

Dataset Information

Dog as a Model for Osteoarthritis: The FGF4 Retrogene Insertion May Matter.

Publications

Dog as a Model for Osteoarthritis: The FGF4 Retrogene Insertion May Matter.

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