Using animal models in osteoarthritis biomarker research.
Osteoarthritis (OA) is a disease that commonly affects human and veterinary patients. Animal models are routinely used for OA research, and the dog is a nearly ideal species for translational investigation of human OA biomarkers. The cytokine, chemokine, and matrix metalloprotease (MMP) profiles of synovial fluid, serum, and urine from dogs with surgically induced and naturally occurring OA were compared with dogs without OA using xMAP technology (Qiagen Inc., Valencia, CA). Markers that exhibited significant differences between groups were identified (monocyte chemoattractant protein 1 [MCP1], interleukin 8 [IL8], keratinocyte-derived chemoattractant [KC], and MMP2 and MMP3), and their sensitivities and specificities were calculated to determine their diagnostic usefulness in a future biomarker panel. Synovial fluid IL8 was the most sensitive, but MCP1 was also highly sensitive and specific. The alterations in KC suggested that it may differentiate between cruciate disease and other types of OA, and the MMPs were most sensitive and specific in the serum. This study provided additional insight to the participation of cytokines, chemokines, and MMPs in OA, and potential diagnostic biomarker candidates were identified. A brief literature review of other biomarker candidates previously examined using animal models is discussed.
Department of Veterinary Pathology, University of Georgia, Athens, GA 30605, USA. garnerb@uga.edu
Bridget C
BC
Garner
Aaron M
AM
Stoker
Keiichi
K
Kuroki
Richard
R
Evans
Cristi Reeves
CR
Cook
James L
JL
Cook
D000818:Animals; D001182:Arthroscopy; D015415:Biomarkers / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein; D018932:Chemokine CCL2; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism* / Q000652:urine; D004195:Disease Models, Animal; D004285:Dogs; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D064235:Matrilin Proteins; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000503:physiopathology; D012680:Sensitivity and Specificity; D013582:Synovial Fluid / Q000737:chemistry / Q000378:metabolism
D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D016209:Interleukin-8; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D020782:Matrix Metalloproteinases