The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases

• Published in: BMC musculoskeletal disorders Vol. 15; no. 1; p. 93
• Main Authors: Sun, Shu, Bay-Jensen, Anne-Christine, Karsdal, Morten A, Siebuhr, Anne Sofie, Zheng, Qinlong, Maksymowych, Walter P, Christiansen, Thorbjørn G, Henriksen, Kim
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19-03-2014; BioMed Central
• Subjects: Amino Acid Sequence; Amino acids; Analysis; Animals; Antibodies, Monoclonal - immunology; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - enzymology; Binding sites; Biomarkers; Blood; C-reactive protein; C-Reactive Protein - analysis; Cartilage - drug effects; Cartilage - enzymology; Cartilage - secretion; Data analysis; Development and progression; Disease; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Female; Hospitals; Humans; Inflammation; Laboratory animals; Male; Matrix Metalloproteinase 3 - blood; Matrix Metalloproteinase 3 - immunology; Matrix Metalloproteinase 3 - secretion; Measurement; Medical examination; Medical law; Medical research; Medicine, Experimental; Mice; Molecular Sequence Data; Musculoskeletal diseases; Oncostatin M - pharmacology; Organ Culture Techniques; Osteoarthritis, Knee - pathology; Peptides; Proteins; Reproducibility of Results; Rheumatic diseases; Rheumatoid arthritis; Sensitivity and Specificity; Severity of Illness Index; Specific Pathogen-Free Organisms; Spondylitis, Ankylosing - blood; Spondylitis, Ankylosing - drug therapy; Spondylitis, Ankylosing - enzymology; Studies; Synovial Membrane - drug effects; Synovial Membrane - enzymology; Synovial Membrane - secretion; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology; Beijing China; China
• ISSN: 1471-2474; 1471-2474
• DOI: 10.1186/1471-2474-15-93

Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treatment. Hence, we aimed to develop a sensitive assay specifically measuring the active form of MMP-3 (act-MMP-3) both in ex vivo models and in human sera.
A monoclonal antibody against the first 6 amino acids of act-MMP-3 was developed, and the specificity was carefully tested by comparing total and active MMP-3. A technically robust act-MMP-3 ELISA was produced. For biological validation, human synovial membrane and human cartilage explant (HEX) culture models were measured and compared by ELISA and immunoblots. For clinical relevance, the serum levels of act-MMP-3 in AS and RA patients before and after anti-TNF-α treatment were evaluated.
A highly specific and technically robust ELISA detecting act-MMP-3 in serum was developed. The lower limit of detection was 33.7 pg/mL. The dilution and spiking recovery of human serum was within 100 ± 20%. The average intra- and inter-assay variations were 3.1% and 13.5% respectively.High levels of act-MMP-3 expression were observed in human synovial membrane culture and oncostatin M and TNF-α stimulated human cartilage. In a cross-sectional study of both AS and RA patients, serum act-MMP-3 level was correlated with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). In addition, in patients receiving anti-TNF-α treatment, the serum level of act-MMP-3 was significantly reduced compared to baseline level reflecting the anti-inflammatory effects of the treatment.
We have successfully developed an assay measuring act-MMP-3 in human serum showing correlation to inflammatory markers. Further studies are required to clarify, whether act-MMP-3 can serve as a predictive marker for outcome in chronic rheumatoid disorders.