Osteoarthritis biomarkers and uses thereof

Abstract

The invention relates to the identification and selection of novel biomarkers and the identification and selection of novel biomarker combinations which are differentially expressed in osteoarthritis and/or in a particular stage of osteoarthritis, as well as a means of selecting the novel biomarker combinations. The measurement of expression of the products of the biomarkers and combinations of biomarkers demonstrates particular advantage in one or more of the following: (a) diagnosing individuals as having arthritis, (b) differentiating between two stages of osteoarthritis (OA) and (c) diagnosing individuals as having a particular stage of OA. Polynucleotides and proteins which specifically and/or selectively hybridize to the products of the biomarkers are within the scope of the invention as are kits containing said polynucleotides and proteins and the use of said polynucleotides and proteins. The biomarker products can be used to identify therapeutic targets for osteoarthritis, and compounds that bind and/or modulate the gene activity.

1 .- 13 . (canceled) 
     
     
         14 . A method of diagnosing osteoarthritis in a test subject, the method comprising: for each gene of a set of genes consisting of alpha glucosidase II alpha subunit (G2AN) and tumor necrosis factor, alpha-induced protein 6 (TNFAIP6), measuring the RNA expression level of the gene in a blood sample of the test subject, wherein measuring the RNA expression level of the gene is done using a polynucleotide which can specifically and/or selectively hybridize with RNA encoded by G2AN, or with DNA complementary to RNA encoded by G2AN. 
     
     
         15 . The method of  claim 14 , further comprising determining a ratio between the RNA expression level of the gene in the sample of the test subject and the RNA expression level of the gene in blood of subjects not having osteoarthritis. 
     
     
         16 . The method of  claim 15 , further comprising measuring the RNA expression level of the gene in blood samples of a population of control subjects not having osteoarthritis, thereby obtaining the RNA expression level of the gene in blood of subjects not having osteoarthritis. 
     
     
         17 . The method of  claim 15 , further comprising diagnosing the test subject as having osteoarthritis if the ratio indicates, for G2AN, that the RNA expression level of the gene in the sample of the test subject is higher than the RNA expression level of the gene in blood of subjects not having osteoarthritis, and, for TNFAIP6, that the RNA expression level of the gene in the sample of the test subject is lower than the RNA expression level of the gene in blood of subjects not having osteoarthritis. 
     
     
         18 . The method of  claim 14 , wherein measuring the RNA expression level of the gene is done by amplification. 
     
     
         19 . The method of  claim 14 , wherein measuring the RNA expression level of the gene is done using the polynucleotides identified as SEQ ID NOs: 51, 52, 55 and 56. 
     
     
         20 . The method of  claim 15 , wherein measuring the RNA expression level of the gene is done using the polynucleotides identified as SEQ ID NOs: 51, 52, 55 and 56. 
     
     
         21 . The method of  claim 16 , wherein measuring the RNA expression level of the gene is done using the polynucleotides identified as SEQ ID NOs: 51, 52, 55 and 56. 
     
     
         22 . The method of  claim 17 , wherein measuring the RNA expression level of the gene is done using the polynucleotides identified as SEQ ID NOs: 51, 52, 55 and 56. 
     
     
         23 . The method of  claim 18 , wherein measuring the RNA expression level of the gene is done using the polynucleotides identified as SEQ ID NOs: 51, 52, 55 and 56.