Osteomodulin and osteomodulin fragments as biomarkers for osteoarthritis and use thereof

Abstract

The present invention refers to osteomodulin (OMD) protein or fragment of osteomodulin (OMD) protein for use in the prognosis and/or diagnosis of osteoarthritis and/or subchondral bone sclerosis of mammals, preferably human individuals. The present invention further refers to a method for prognosis and/or diagnosis of osteoarthritis and/or subchondral bone sclerosis, comprising the following steps: i) measuring osteomodulin (OMD) protein or a fragment or fragments of osteomodulin (OMD) protein in samples of body fluids of mammalian individuals, preferably human serum samples; ii) judging that decreased levels of osteomodulin (OMD) protein or of said fragment(s) compared to levels in body fluids, preferably serum, of healthy individuals indicate onset of osteoarthritis and/or subchondral bone sclerosis. The present invention also provides an immunological binding partner specifically binding to osteomodulin (OMD) protein or fragment of osteomodulin (OMD) protein for use in the prognosis and/or diagnosis of osteoarthritis and/or subchondral bone sclerosis of mammals, preferably human individuals and a kit comprising said immunological binding partner.

1 . A method of detecting Osteomodulin (OMD) protein or fragment of osteomodulin (OMD) protein in mammals, preferably human individuals, comprising the step of measuring concentration of said osteomodulin protein or its fragment(s) in body fluids. 
     
     
         2 . The method according to  claim 1 , wherein decreased expression or decreased concentration in body fluids of said osteomodulin protein or its fragment(s) compared to healthy individuals indicate onset of osteoarthritis and/or subchondral bone sclerosis. 
     
     
         3 . The method according to  claim 2 , wherein said decreased expression or decreased concentration is measured in body fluids selected from the group consisting of urine, secretions, interstitial fluid, blood, synovial fluid, serum, spinal fluid lymph, preferably serum. 
     
     
         4 . The method according to  claim 1 , wherein full-length osteomodulin protein is having the amino acid sequence shown in SEQ ID NO: 1,
 wherein osteomodulin (OMD) protein is a protein represented by the amino acid positions 1-421 or by the amino acid positions 21-421 of SEQ ID NO: 1; and wherein said fragment is selected from the group consisting a) to f):   a) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 21 to 148 and having C-terminal amino acid residue varying from amino acid position 162 to 235 in the amino acid sequence shown in SEQ ID NO: 1;   b) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 224 to 261 and having C-terminal amino acid residue varying from amino acid position 276 to 421 in the amino acid sequence shown in SEQ ID NO: 1;   c) OMD-(131-223),   d) OMD-(236-296),   e) OMD-(148-162),   f) OMD-(261-276).   
     
     
         5 . The method according to  claim 1 , wherein full-length osteomodulin protein is having the amino acid sequence shown in SEQ ID NO: 1,
 wherein osteomodulin (OMD) protein is a protein represented by the amino acid positions 1-421 or by the amino acid positions 21-421 of SEQ ID NO: 1; and wherein said fragment is selected from the group consisting a) to f):   a) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 131 to 148 and having C-terminal amino acid residue varying from amino acid position 162 to 223 in the amino acid sequence shown in SEQ ID NO: 1;   b) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 236 to 261 and having C-terminal amino acid residue varying from amino acid position 276 to 296 in the amino acid sequence shown in SEQ ID NO: 1;   c) OMD-(131-223),   d) OMD-(236-296),   e) OMD-(148-162),   f) OMD-(261-276).   
     
     
         6 . The method according to  claim 4 , wherein the fragment according to  4  a), c) and e) is specifically bound by an immunological binding partner raised against OMD-(148-162). 
     
     
         7 . The method according to  claim 4 , wherein the fragment according to  claim 4  b),  4  d) and f) is specifically bound by an immunological binding partner raised against OMD-(261-276). 
     
     
         8 . A method for prognosis and/or diagnosis of osteoarthritis and/or subchondral bone sclerosis, comprising the following steps:
 i) measuring osteomodulin (OMD) protein or a fragment or fragments of osteomodulin (OMD) protein in samples of body fluids of mammalian individuals, preferably human serum samples;   ii) judging that decreased levels of osteomodulin (OMD) protein or of said fragment(s) compared to levels in body fluids, preferably serum, of healthy individuals indicate onset of osteoarthritis and/or subchondral bone sclerosis.   
     
     
         9 . A method for determining or checking or diagnosis of the therapeutic effect of treatment of osteoarthritis and/or subchondral bone sclerosis in a mammalian individual, preferably a human individual, comprising the following steps:
 i) measuring osteomodulin (OMD) protein or a fragment or fragments of osteomodulin (OMD) protein in samples of body fluids, preferably serum samples, of said individual during or after treatment;   ii) judging that either one of (1) to (3)   (1) normal levels of osteomodulin (OMD) protein or of said fragment(s) in the samples obtained in step i), or   (2) increased levels of osteomodulin (OMD) protein or of said fragment(s) in said samples obtained in step i) compared to levels in samples of body fluids, preferably serum samples, of said individual before said treatment, or   (3) increased levels of osteomodulin (OMD) protein or of said fragment(s) in said samples obtained in step i) compared to levels in samples of body fluids, preferably serum samples, of healthy individuals, indicate a therapeutic effect of the treatment of osteoarthritis and/or subchondral bone sclerosis in said individual.   
     
     
         10 . The method according to  claim 8 , wherein full-length osteomodulin protein is having the amino acid sequence shown in SEQ ID NO: 1,
 wherein osteomodulin (OMD) protein to be measured in step i) is a protein represented by the amino acid positions 1-421 or by the amino acid positions 21-421 of SEQ ID NO: 1; and   wherein said fragment to be measured in step i) is selected from the group consisting a) to f):   a) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 21 to 148 and having C-terminal amino acid residue varying from amino acid position 162 to 235 in the amino acid sequence shown in SEQ ID NO: 1; b) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 224 to 261 and having C-terminal amino acid residue varying from amino acid position 276 to 421 in the amino acid sequence shown in SEQ ID NO: 1;   c) OMD-(131-223),   d) OMD-(236-296),   e) OMD-(148-162),   f) OMD-(261-276).   
     
     
         11 . The method according to  claim 8 , wherein full-length osteomodulin protein is having the amino acid sequence shown in SEQ ID NO: 1,
 wherein osteomodulin (OMD) protein to be measured in step i) is a protein represented by the amino acid positions 1-421 or by the amino acid positions 21-421 of SEQ ID NO: 1; and   wherein said fragment to be measured in step i) is selected from the group consisting a) to f):   a) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 131 to 148 and having C-terminal amino acid residue varying from amino acid position 162 to 223 in the amino acid sequence shown in SEQ ID NO: 1;   b) osteomodulin fragment having N-terminal amino acid residue varying from amino acid position 236 to 261 and having C-terminal amino acid residue varying from amino acid position 276 to 296 in the amino acid sequence shown in SEQ ID NO: 1;   c) OMD-(131-223),   d) OMD-(236-296),   e) OMD-(148-162),   f) OMD-(261-276).   
     
     
         12 . The method according to  claim 10 , wherein the fragment according to  10  a),  10 c) and  10 e) is specifically bound by an immunological binding partner raised against OMD-(148-162); and/or
 wherein the fragment according to  10  b),  10 d) and  10 f) is specifically bound by an immunological binding partner raised against OMD-(261-276). 
 
     
     
         13 . The method according to  claim 10 , wherein at least two osteomodulin fragment species are measured, namely any one of  10  a),  10 c) and  10 e) and any one of  10  b),  10 d) and  10 f). 
     
     
         14 - 15 . (canceled) 
     
     
         16 . Immunological binding partner specifically binding to osteomodulin (OMD) protein or fragment of osteomodulin (OMD) protein for use in the prognosis and/or diagnosis of osteoarthritis and/or subchondral bone sclerosis of mammals, preferably human individuals. 
     
     
         17 - 19 . (canceled) 
     
     
         20 . The method according to  claim 5 , wherein the fragment according to  5  a), c) and e) is specifically bound by an immunological binding partner raised against OMD-(148-162). 
     
     
         21 . The method according to  claim 5 , wherein the fragment according to  5 b),  5 d) and  5 f) is specifically bound by an immunological binding partner raised against OMD-(261-276). 
     
     
         22 . The method according to  claim 11 , wherein the fragment according to claim  11 a),  11 c) and  11 e) is specifically bound by an immunological binding partner raised against OMD-(148-162); and/or
 wherein the fragment according to  11 b),  11 d) and  11 f) is specifically bound by an immunological binding partner raised against OMD-(261-276).   
     
     
         23 . The method according to  claim 11 , wherein at least two osteomodulin fragment species are measured, namely any one of  11  a),  11  c) and  11 e), and any one of  11  b),  11 d) and  11 f). 
     
     
         24 . (canceled) 
     
     
         25 . The method according to  claim 4 , wherein the osteomodulin (OMD) protein fragment comprises both OMD1 and OMD2 and represents more than half of the entire osteomodulin protein.