Analysis of Cartilage Oligomeric Matrix Protein (COMP) in Synovial Fluid, Serum and Urine from 51 Racehorses with Carpal Bone Fracture

Abstract

ABSTRACT. We investigated the relationship between cartilage oligomeric matrix protein (COMP) levels in synovial fluid (SF), serum and urine and the development of osteochondral damage and osteophyte (OP) formation following intraarticular fractures of the carpus in racehorses in order to assess the clinical usefulness of COMP as a diagnostic biomarker of developmental osteoarthritis (OA). Two monoclonal antibodies (mAb clones 2A11 and 3C8) raised against equine COMP were shown to be capable of detecting the molecule in serum and urine as well as SF. Fifty-one samples were obtained from 26 OP-positive (OP(+)) and 25 OP-negative (OP(-)) racehorses with carpal bone fracture, in whom OP was ascertained arthroscopically and radiographically. The COMP measurements obtained using the two mAbs were highly correlated with each other in SF, serum, or urine. Horses with OP(+) showed a significantly higher [urinary COMP (µg)]/[urinary creatinine (mg)] ratio (4.94 ± 5.10 and 1.46 ± 1.19, using mAbs 2A11 and 3C8, respectively) than OP(-) horses (2.80 ± 1.72 and 0.93 ± 0.49, respectively). The relationship between serum and urine COMP levels and the period from injury to surgery were extrapolated using a polynomial expression. Measurement of COMP, especially in urine, has potential as a predictive marker of advanced OA following carpal bone fractures in racehorses. KEY WORDS: COMP, equine, fracture, osteoarthritis, urine.J. Vet. Med. Sci. 70(9): 915-921, 2008 Cartilage oligomeric matrix protein (COMP), an abundant non-collagenous extracellular matrix protein in cartilage [1], plays an important role in the construction of collagen bundles and networks, being likely involved in determination of fibril diameter and/or orientation [2,3] and interaction with other extracellular matrix molecules [4]. A recent study has also suggested that association of COMP with granulin-epithelin precursor could be required for chondrocyte proliferation [5]. COMP may also play a role in the pathogenesis of osteoarthritis (OA) as a factor secreted by chondrocytes to ameliorate matrix breakdown at the late stage of OA [6]. In human OA, measurement of COMP in serum and synovial fluid (SF) has been proposed as a helpful biomarker for predicting disease-mediated damage to joint cartilage [7,8]. The serum COMP level is reportedly higher in patients with OA than in healthy volunteers [9]. The serum level of COMP is significantly correlated with the Western Ontario and McMaster Universities index pain scale for the lower limbs, and is higher in patients with bilateral knee OA than in unilaterally affected patients [10]. Another study has suggested that serum COMP level at the baseline could be useful for predicting the course of OA, progressors showing higher average values than nonprogressors [11].In studies of horses, we have demonstrated enhanced degradation of COMP in SF, and suggested that COMP fragmentation in SF could be useful for monitoring equine OA in combination with ELISA measurements [12]. Subsequently, we investigated the clinical use...

Gambling on putative biomarkers of osteoarthritis and osteochondrosis by equine synovial fluid proteomics

“…A similar condition was verified for collagen type I and II fragments, prostaglandin E2, osteocalcin, glycosaminoglycans, hyaluronic acid (HA) and proteins related to cartilage turnover, i.e. cartilage oligomeric matrix protein (COMP), matrix metalloproteinases (MMPs) and disintegrin-metalloproteinases with thrombospondin motifs (ADAMTs), [14,[19][20][21][22][23][24][25][26]. Some of these molecules have also been proposed as OC biomarkers [10,14,[27][28][29], but with the limitations mentioned above [14].…”

Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury

“…Factors such as chronicity, exercise, and previous medical treatments were mostly unknown. Although this is not an uncommon problem when examining clinical cases of naturally occurring joint disease for biomarker studies, 14,18,25,26,[33][34][35][36][37][38][39] the potential effect on biomarker concentrations can be quite profound. For example, administration of phenylbutazone, 40 lidocaine, 41 methylprednisolone acetate, 42 and triamcinolone acetonide 43 results in changes in biomarker concentrations in equine joints.…”

Cartilage oligomeric matrix protein and matrix metalloproteinase-3 expression in the serum and joint fluid of a reversible osteoarthritis rabbit model

“…Articular cartilage destruction mainly happens in two ways: the cartilage extracellular matrix is degraded by the cartilage cells themselves or the cartilage extracellular matrix is damaged by invasive inflammatory cells, pannus tissue, or inflammatory synovium through the joint synovial fluid. The main factor in cartilage damage is the enzymatic degradation of the extracellular matrix (Arai et al, 2008;Posey and Hecht, 2008). It has been suggested (Posey and Hecht, 2008) that matrix metalloproteinases (MMPs) play an important role in the injury of articular cartilage, while MMP-3 is one of the most important enzymes among the articular cartilage matrixdegrading enzymes.…”