Cartilage gene expression correlates with radiographic severity of canine elbow osteoarthritis Dylan N. Clements a,b, * , Noel Fitzpatrick c , Stuart D. Carter a , Philip J.R. Day b a Musculoskeletal Research Group, Department of Veterinary Pathology, Faculty of Veterinary Science, University of Liverpool, Liverpool L69 3BX, UK b Centre for Integrated Genomic Medical Research, The Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK c Fitzpatrick Referrals, Farnham, Surrey GU2 9AD, UK Accepted 29 August 2007 Abstract The relationship between radiographic measures of severity of osteoarthritis (OA) and changes in gene expression in joints are not well characterised. In this study, the expression of 11 candidate genes was characterised by quantitative reverse transcriptase polymerase chain reaction in normal and OA cartilage and bone from the elbows of dogs with fragmented coronoid disease. The levels of expression of type I collagen a2 chain (COL1A2), type III collagen a1 chain (COL3A1), lumican (LUM), matrix metalloproteinase-2 (MMP2), -9 (MMP9) and -13 (MMP13) genes were increased and the expression of tissue inhibitor of metalloproteinase-2 (TIMP2) and cathepsin D (CTSD) genes were decreased in OA cartilage relative to normal cartilage. All differences correlated with radiographic measures of sever- ity of OA. Levels of expression of COL1A2, MMP2, MMP9, MMP13 and TIMP1 were increased, whereas expression of TIMP2 was decreased in OA bone relative to normal bone. Cartilage gene expression may be correlated with the radiographic severity of OA. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Osteoarthritis; Canine; Cartilage; Bone; Gene expression; Collagen; Lumican; Matrix metalloproteinase; TIMP; Cathepsin Introduction Osteoarthritis (OA) is characterised by destruction of articular cartilage, although other tissues, such as bone (Rogers et al., 2004), synovium (Dingle, 1981), fat (Ushiy- ama et al., 2003) and ligament (Hill et al., 2005), are also changed in OA joints and may be involved in the pathogen- esis of the disease. Up to 17.8% of dogs in purebred popu- lations have radiographic evidence of elbow OA (Morgan et al., 1999), often secondary to other primary processes, such as fragmented medial coronoid process (FCP). FCP is a disease of elbow joints that results in changes in the bony architecture of the medial coronoid process of the elbow (Danielson et al., 2006), invariably leading to the development of secondary OA. It is the primary cause of elbow lameness and elbow OA in dogs (van Ryssen and van Bree, 1997). The pathogenesis of medial coronoid fragmentation is unknown, although the observation of micro-crack damage and increased porosity in affected bone suggests that the osteochondral fragment develops from chronic fatigue damage to the bone (Danielson et al., 2006). These microscopic changes in bone structure also are the hallmark of OA bone (Dedrick et al., 1997; Fazzalari et al., 1998). Although FCP can occur in the absence of macroscopic evidence of OA (Guthrie et al., 1992), the bone pathology that characterises the disease may represent OA per se. The importance of bone in the pathogenesis of OA has been recognised, with some authors suggesting that OA may be primarily a disease of the skeleton (Rogers et al., 2004). Bone changes, such as increases in subchondral bone density and activity (Brandt et al., 1991), have been 1090-0233/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2007.08.027 * Corresponding author. Present address: The Royal (Dick) School of Veterinary Science Hospital for Small Animals, University of Edinburgh, Easter Bush Veterinary Centre, Roslin EH25 9RG, UK. Tel.: +44 151 7942000; fax: +44 151 7944219. E-mail address: dylan.clements@ed.ac.uk (D.N. Clements). www.elsevier.com/locate/tvjl Available online at www.sciencedirect.com The Veterinary Journal 179 (2009) 211–218 The Veterinary Journal