{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:21:33Z","timestamp":1771230093304,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T00:00:00Z","timestamp":1565654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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\u2010chondrodystrophic (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 (<jats:italic>FGF4<\/jats:italic>) 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\u2010 and NCD\u2010derived cartilage differs on a structural and biochemical level, and to explore the relationship between <jats:italic>FGF4<\/jats:italic> 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\u20102) 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\u20103 gene expression was higher in NCD cartilage. No differences in other Wnt pathway read outs were found. To conclude, chondrodystrophy associated with the <jats:italic>FGF4<\/jats:italic> 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.  \u00a9 2019 The Authors. <jats:italic>Journal of Orthopaedic Research<\/jats:italic><jats:sup>\u00ae<\/jats:sup> Published by Wiley Periodicals, Inc. 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