Soluble biomarkers of cartilage and bone metabolism in early proof of concept trials in psoriatic arthritis: Effects of adalimumab versus placebo

Background: There is growing interest in soluble biomarkers that could be used on the group level for screening purposes in small proof of principle studies during early drug development. We investigated early changes in serum levels of several candidate biomarkers involved in cartilage and bone metabolism following the initiation of adalimumab...

Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content

Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in...

Effect of collagen turnover and matrix metalloproteinase activity on healing of venous leg ulcers

Background: The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and normal skin. Methods: Biopsies were taken from the...

Matrix metalloproteinases in premature coronary atherosclerosis: Influence of inhibitors, inflammation, and genetic polymorphisms

Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly in the occurrence of acute coronary syndrome (ACS). Little is known about human in vivo MMP regulation in CAD. The expression and regulation of MMPs and their tissue inhibitors (TIMPs) were evaluated in premature CAD....

Effect of the anti-tumor necrosis factor-α antibody infliximab on the ex vivo mucosal matrix metalloproteinase-proteolytic phenotype in inflammatory bowel disease

Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-α antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9,...

Gingival tissue and crevicular fluid co-operation in adult periodontitis

Activated matrix metalloproteinase-3 (MMP-3) can contribute to periodontal ligament destruction in adult periodontitis. Since MMP-3 has been reported to activate proMMP-8 and -9, it was speculated that gingival tissue fibroblast-derived MMP-3 might, in periodontitis, be responsible for activation of gingival crevicular fluid (GCF) neutrophil...

Glucosamine decreases expression of anabolic and catabolic genes in human osteoarthritic cartilage explants

Objective: To investigate the effect of glucosamine (GlcN) in a human osteoarthritic explant model on expression of genes involved in anabolic and catabolic activities of chondrocytes. Methods: Human osteoarthritic explants, obtained during knee arthroplasty surgery, were pre-cultured (3 days) and treated with glucosamine-hydrochloride (GlcN-HCl...

MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis

Objective: To determine protein and activity levels of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) in synovial fluid of patients with knee joint injury, primary osteoarthritis, and acute pyrophosphate arthritis (pseudogout). Methods: Measurements were done on knee synovial fluid obtained in a cross sectional study of cases of injury (n...

MMP profile in paired serum and synovial fluid samples of patients with rheumatoid arthritis

Objective: To analyse matrix metalloproteinases (MMPs) and tissue inhibitor-1 of MMPs (TIMP-1) levels in the systemic circulation and synovial fluid (SF) of patients with RA and to compare these levels with inflammatory and collagen degradation markers. Methods: ProMMP-1, -2, -3, -8, -9, TIMP-1, levels of MMP/ α2-macroglobulin complexes, and...

Matrix metalloproteinases-3, -8, -9 as markers of disease activity and joint damage progression in early rheumatoid arthritis

Objective: To analyse the relation between systemic levels of pro-MMP-3, -8, and -9 matrix metalloproteinase (MMP) activity in α2 macroglobulin (α2M)/MMP complexes and the progression of joint destruction in patients with recent onset rheumatoid arthritis (RA). Methods: 109 patients with RA of recent onset were entered into this longitudinal...

The canine 'groove' model, compared with the ACLT model of osteoarthritis

Objective: The frequently used anterior cruciate ligament transection (ACLT) model of osteoarthritis (OA) in the dog, makes use of a permanent trigger (joint instability) for inducing degenerative changes. The present study evaluates a canine model of degenerative cartilage damage, mimicking OA, which is induced without making use of permanent...

Invasive properties of fibroblast-like synoviocytes Correlation with growth characteristics and expression of MMP-1 MMP-3 and MMP-10

Background: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). Objective: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with arthritis in relation to the expression of MMP 1...

Temporal changes in collagen composition and metabolism during rodent palatogenesis

Cleft lip and palate is a common craniofacial malformation in man. The aetiology is multifactorial and not known. Since collagen is a major structural component of the developing palate, we studied its composition and metabolism during palate shelf formation and elevation in the rat. Palatal shelves were harvested at embryonic days (E) 15, 16...

Influence of development and joint pathology on stromelysin enzyme activity in equine synovial fluid

Objective - To investigate the role of stromelysin (MMP-3) activity in synovial fluid (SF) at different stages of development and in common joint disorders in the horse. Methods - Stromelysin activity was determined with a fluorogenic enzyme activity assay in SF of normal joints of fetal, juvenile and adult horses, and in SF of horses suffering...

Highly increased levels of active stromelysin in rheumatoid synovial fluid determined by a selective fluorogenic assay

Stromelysin-1 (MMP-3) is an important member of the matrix metalloproteinase family. In joint-degrading diseases like arthritis, elevated levels of MMP-3 protein are detected in synovial fluid using immunological methods. However, these methods do not discriminate between active and inactive enzyme. In the present study, a specific stromelysin...

Regulation of plasminogen activation, matrix metalloproteinases and urokinase-type plasminogen activator-mediated extracellular matrix degradation in human osteosarcoma cell line MG63 by interleukin-1 alpha

Plasmin-mediated extracellular proteolysis has been implicated in the degradation of bone in normal and pathological conditions. Normal and malignant osteoblasts can produce both tissue-type plasminogen activator (t- PA) and urokinase-type plasminogen activator (u-PA). We have used the osteosarcoma cell line MG63 to address the question of...