title: Alterations in sclerostin protein in lesions of equine osteochondrosis.
abstract: Osteochondrosis (OC) is a common and clinically important joint disease that occurs in many species, including humans, pigs, chickens and horses. It has been described as a focal failure of endochondral ossification (EO), but no cellular/molecular mechanisms are fully described that explain the cause of this condition. Recently a Wnt signalling inhibitor, sclerostin, has been described in osteoarthritic cartilage, where it has been proposed to protect damaged cartilage from degradation. Cartilage degradation is a key event in EO, thus, abnormalities of sclerostin in growth cartilage could, potentially, lead to a failure of EO and, thus, OC. The aim of this study was to describe the distribution of sclerostin protein in normal and OC growth cartilage. Immunohistochemistry (IHC) was used to localise sclerostin protein in normal and OC growth cartilage. Growth cartilage was harvested from the distal femur of horses aged between 6 and 18 months. Cartilage was classified as normal or having lesions consistent with a diagnosis of early OC. IHC was used to identify sclerostin protein in cartilage sections. Sclerostin protein distribution was semiquantified using a grading system and shown to be upregulated throughout all three zones of cartilage in lesions of OC (IHC score 8.1 compared to IHC score of 0.88). These results indicate that sclerostin may be contributing to the development of OC lesions by inhibiting extracellular matrix remodelling or may reflect the response of damaged cartilage. Clearly, further work is required to fully characterise this observation but, with antisclerostin antibodies used to treat human osteoporosis, the possibility of development of a systemic treatment of OC remains a potential goal.
authors.affiliation: Orthopaedic Research Unit , University of Cambridge, Addenbrooke's Hospital , Box 180, Hill's Road, Cambridge CB2 2QQ , UK.
authors.forename: Jonathon
authors.initials: J
authors.lastname: Power
authors.affiliation: Orthopaedic Research Unit , University of Cambridge, Addenbrooke's Hospital , Box 180, Hill's Road, Cambridge CB2 2QQ , UK.
authors.forename: Paula
authors.initials: P
authors.lastname: Hernandez
authors.affiliation: Orthopaedic Research Unit , University of Cambridge, Addenbrooke's Hospital , Box 180, Hill's Road, Cambridge CB2 2QQ , UK.
authors.forename: John
authors.initials: J
authors.lastname: Wardale
authors.affiliation: Orthopaedic Research Unit , University of Cambridge, Addenbrooke's Hospital , Box 180, Hill's Road, Cambridge CB2 2QQ , UK.
authors.forename: Frances M D
authors.initials: FM
authors.lastname: Henson
keywords: Horses; Joint Diseases; Orthopaedics