MMP-3 in the peripheral serum as a biomarker of knee osteoarthritis, 40 years after open total knee meniscectomy.

BACKGROUND: To explore potential biomarkers in a meniscectomy-induced knee osteoarthritis model, at forty years after meniscectomy. METHODS: We carried out a forty-year study of 53 patients who, as adolescents, underwent open total meniscectomy and assessed two potential synovial and serum biomarkers, namely glycosaminoglycan (GAG) and matrix metalloproteinase-3 (MMP-3). Of the 30 patients available for review, 8 had contralateral knee operations and were excluded. Of the remaining 22 patients, 17 had successful operated knee synovial fluid aspirations and 8 also had successful contralateral control knee aspirations. GAG and MMP3 levels in the synovial fluid and peripheral serum was measured using Alcian blue precipitation and ELISA quantification, respectively. Patients also had their knee radiographs assessed and their radiographic osteoarthritis classified as per the Kellgren-Lawrence and Ahlbӓck systems. RESULTS: At forty years after meniscectomy, synovial MMP-3 levels remain increased (p = 0.0132) while GAG levels were reduced (p = 0.0487) when compared to controls and these two levels correlate inversely. Furthermore, levels of synovial MMP-3 significantly correlated (p = 0.0032, r = 0.7734; p = 0.0256, r = 0.5552) and GAG levels significantly inversely correlated (p = 0.0308, r = - 0.6220; p = 0.0135, r = - 0.6024), respectively, with both radiological scoring systems. Interestingly, we found that the levels of serum MMP-3 correlated only with the synovial fluid levels of MMP-3 in the operated knee and not with the non-operated joint (p = 0.0252, r = 0.7706 vs. p = 0.0764, r = 0.6576). Multiple regression analysis for patient's quality of life based on these biomarkers revealed an almost perfect result with an R2 of 0.9998 and a p value = 0.0087. CONCLUSION: Our results suggest that serum levels of MMP3 could be used as a potential biomarker for knee osteoarthritis, using a simple blood test. Larger cohorts are desirable in order to prove or disprove this finding

Modern NMR spectroscopy of proteins and peptides in solution and its relevance to drug design

The knowledge of the three-dimensional (3D) structures and conformational dynamics of proteins and peptides is important for the understanding of biochemical and genetic data derived for these molecules. This understanding can ultimately be of help in drug design. We describe here the role of Nuclear Magnetic Resonance (NMR) spectroscopy in this process for three distinct situations: for small proteins, where relatively simple NMR methods can be used for full 3D structure determination; for larger proteins that require multinuclear multidimensional NMR but for which full 3D structures can still be obtained; and for small peptides that are studied in interaction with macromolecules (receptors) using specialized NMR techniques. A fourth situation, pertaining to large systems where only partial structural information can be obtained from NMR data, is briefly discussed. Molecules of interest to the biomedical field (C5a and stromelysin) are discussed as examples.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43356/1/11091_2005_Article_BF02174537.pd

Cartilage matrix metabolism in osteoarthritis : markers in synovial fluid, serum, and urine

Osteoarthritis is a major cause of disability and early retirement. Yet we lack the means to diagnose the disease in its early stages or to monitor the effects of treatment on the target tissue, the joint cartilage. Neither can we identify the disease mechanisms at the tissue or cell level. Current research focuses on the use of markers of cartilage matrix metabolism in body fluids as a means to diagnose and monitor osteoarthritis. Cartilage proteoglycan, collagen and glycoprotein fragments, as well as proteinases and their inhibitors, are being suggested for this purpose. Structural information on matrix molecule fragments released into body fluids may also help to identify the enzymes active in the destruction of the cartilage, a central issue in osteoarthritis