Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation.
We determined the tissue distribution of cartilage oligomeric matrix protein (COMP) in man and evaluated COMP in synovial fluid (SF) and serum. COMP was purified from human articular cartilage. Polyclonal antibodies were used to detect COMP in tissue cryosections and protein extracts. COMP was determined quantitatively and qualitatively in SF and serum by competitive enzyme-linked immunosorbent assay and immunoblotting. Knee joint SF was taken from nine cadaveric and six living controls, 52 patients with osteoarthritis (OA), 85 patients with rheumatoid arthritis (RA) and 60 patients with other forms of inflammatory arthritis. The degradative potential of SF on native COMP was tested in vitro. The highest concentrations of COMP were measured in articular cartilage and meniscus, the lowest in rib and trachea. Compared with controls, the concentrations of COMP in SF and serum were elevated in 36 and 50% of the patients. A total of 84% of patients with RA and 60% of patients with other forms of inflammatory arthritis showed significant amounts of low-molecular-weight COMP fragments (50-70 kDa) in SF. In contrast, SF fragments were present in only 21% of the OA patients. Furthermore, 13% of SF taken from patients with RA or other forms of inflammatory arthritis were able to degrade COMP in vitro. Using inhibitors, the involvement of serine proteinases could be demonstrated in only 8% of the cases. Based on these results, the absolute levels of COMP in SF and serum, and its fragmentation pattern in SF, seem to be promising as markers of joint tissue metabolism.
Neidhart
M
M
Department of Rheumatology, University Hospital Zürich, Switzerland.
Hauser
N
N
Paulsson
M
M
DiCesare
P E
PE
Michel
B A
BA
Häuselmann
H J
HJ
D000328:Adult; D000368:Aged; D001168:Arthritis / Q000097:blood / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D064235:Matrilin Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism*
D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D015842:Serine Proteinase Inhibitors; C577553:TSP5 protein, human