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Abstract A central feature of the osteoarthritis (OA) involves erosive destruction of the articular cartilage extracellular matrix (ECM) on the surfaces of joints. The resultant loss of joint function makes studies on mechanisms underlying ECM degradation critical for treatment of the disease and prevention of disability. In the present study serum and synovial fluid samples were collected from normal (n=20), Early OA (n=10) and Late OA (n=20) adult male horses attended from surgery clinic, faculty of veterinary medicine Cairo University. The concentrations of total (TGAGs), individual (CS) and non sulphated (HA) glycosaminoglycans, Procollagen IIC-propeptide (PIICP) and Tartarate resistant acid phosphatase(TRAP) activities were estimated in serum and synovial fluid .The activities of different types of matrix metalloproteinases (MMPs) and tissue inhibitor metalloproteinases (TIMPs) in synovial fluid were estimated by Substrate and Reverse zymography respectively and the expression of MMP-13 was determined by Western blot. The allele and genotype frequencies of the Growth differentiation factor 5(GDF5) and Asporin (ASPN) genes were estimated by PCR-SSCP. The concentrations of TGAGs, CS were significantly increased in different stages of OA, while HA concentration significantly decreased in synovial fluid of OA horses. The activity of pro and active form of MMP-9, level of PIICP and TRAP significantly increased in early stage of OA. While the activity of both proMMP-2 and active MMP-13 as well as level of expression of the later one increased significantly in late stage of OA. In addition, the activity of TIMP-1 significantly decreased in different stages of OA. Three genotypes were determined in GDF5 gene core promoter (AA, BB, and BC) and three genotypes (DD, EE, and DE) were determined in ASPN gene exon-9. In conclusions, GAGs, TRAP, PIICP, MMPs, TIMPs and genetic predisposition; such biomarkers could be used to predict and monitor osteoarthritis pathogenesis. |