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 biomarkers of the invention may be utilized to diagnose arthritis, differentiate between two stages of osteoarthritis and diagnose a particular stage of osteoarthritis. The invention provides kits comprising polynucleotides and/or proteins which specifically and/or selectively hybridize to the products of the biomarkers of the invention. Such kits are useful in diagnosing arthritis, differentiating between two stages of osteoarthritis, diagnosing a particular stage of osteoarthritis monitoring disease progression, and monitoring the efficacy of therapeutic regimens. The invention also provides for methods of using the products of the biomarkers of the invention in the identification of novel therapeutic targets for osteoarthritis.

1 . A composition comprising a collection of two or more isolated proteins which bind selectively to the protein products of at least two biomarkers, wherein the biomarkers are selected from the group consisting of the genes Beta-2-microglobulin, Alpha glucosidase II alpha subunit, Interleukin 13 receptor alpha 1, Inhibitor of kappa light polypeptide gene enhancer in B-cells kinase complex-associated protein, Tumor necrosis factor alpha-induced protein 6, WD repeat domain 9, Nedd-4-like ubiquitin-protein ligase, B-cell CLL/lymphoma 6, Complement component 1q subcomponent receptor 1, Cyclin C, Chromosome 6 open reading frame 151, Heat shock 90 kDa protein 1 alpha, Laminin gamma 1 and PABP-interacting protein, Interferon Regulatory Factor 1, Nuclear receptor coactivator 1, Homo sapiens chloride intracellular channel 4, ATP-binding cassette, sub-family A (ABC 1), member 1 (ABCA1), and ATP-binding cassette, sub-family G (WHITE), member 1, as set out in  FIG. 1 .  
     
     
         2 . A composition comprising a collection of two or more isolated polynucleotides which bind selectively to the RNA products of at least two biomarkers, wherein the biomarkers are selected from the group consisting of the genes Beta-2-microglobulin, Alpha glucosidase II alpha subunit, Interleukin 13 receptor alpha 1, Inhibitor of kappa light polypeptide gene enhancer in B-cells kinase complex-associated protein, Tumor necrosis factor alpha-induced protein 6, WD repeat domain 9, Nedd-4-like ubiquitin-protein ligase, B-cell CLL/lymphoma 6, Complement component 1q subcomponent receptor 1, Cyclin C, Chromosome 6 open reading frame 151, Heat shock 90 kDa protein 1 alpha, Laminin gamma 1 and PABP-interacting protein, Interferon Regulatory Factor 1, Nuclear receptor coactivator 1, Homo sapiens chloride intracellular channel 4, ATP-binding cassette, sub-family A (ABC1), member 1 (ABCA1), and ATP-binding cassette, sub-family G (WHITE), member 1, as set out in  FIG. 1 .  
     
     
         3 . A composition comprising a collection of two or more isolated proteins which bind selectively to the protein products of at least two biomarkers, wherein the biomarkers are selected from the group consisting of the genes Tumor necrosis factor alpha-induced protein 6, WD repeat domain 9, Alpha glucosidase II alpha subunit and the inhibitor of kappa light polypeptide gene enhancer in B-cells kinase complex-associated protein, as set out in  FIG. 2 .  
     
     
         4 . A composition comprising a collection of two or more isolated polynucleotides which bind selectively to the RNA products of at least two biomarkers, wherein the biomarkers are selected from the group consisting of the genes Tumor necrosis factor alpha-induced protein 6, WD repeat domain 9, Alpha glucosidase II alpha subunit and the inhibitor of kappa light polypeptide gene enhancer in B-cells kinase complex-associated protein, as set out in  FIG. 2 .  
     
     
         5 . A composition comprising a collection of isolated proteins which bind selectively to the protein products of biomarkers, wherein the biomarkers are genes Zinc finger RNA binding protein and WD repeat domain 9, as set out in  FIG. 3 .  
     
     
         6 . A composition comprising a collection of isolated polynucleotides which bind selectively to the RNA products of biomarkers, wherein the biomarkers are genes Zinc finger RNA binding protein and WD repeat domain 9, as set out in  FIG. 3 .  
     
     
         7 . A composition comprising a collection of two or more isolated proteins which bind selectively to the protein products of at least two biomarkers, wherein the biomarkers are selected from the group consisting of the genes Period 1 (Drosophila), EBNA1 binding protein 2, Chromosome 6 open reading frame 151 and Laminin gamma 1, as set out in  FIG. 4 .  
     
     
         8 . A composition comprising a collection of two or more isolated polynucleotides which bind selectively to the RNA products of at least two biomarkers, wherein the biomarkers are selected from the group consisting of the genes Period 1 (Drosophila), EBNA1 binding protein 2, Chromosome 6 open reading frame 151 and Laminin gamma 1, as set out in  FIG. 4 .  
     
     
         9 . The composition of  claim 1 ,  3 ,  5 , or  7 , wherein the isolated proteins are ligands.  
     
     
         10 . The composition of  claim 1 ,  3 ,  5 , or  7 , wherein the ligands are antibodies.  
     
     
         11 . The composition of  claim 10 , wherein the antibodies are monoclonal antibodies.  
     
     
         12 . The composition of  claim 2 ,  4 ,  6  or  8 , wherein the isolated polynucleotides are single or double stranded RNA.  
     
     
         13 . The composition of  claim 2 ,  4 ,  6  or  8 , wherein the isolated polynucleotides are single or double stranded DNA.