Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-11-3
pubmed:abstractText
The hypothesis of the present work was that the pannus tissue overlying the articular hard tissues has an aggressive phenotype and contains the newly discovered collagenase-3 and its endogenous inducers and activators. We therefore analyzed the eventual presence of collagenase-3 and its regulation at the pannus-cartilage junction. Collagenase-3 mRNA (in situ hybridization) and enzyme protein (ABC and immunofluorescence staining) were found in the pannocytes in the pannus-hard tissue junction. Inflammatory round cells associated with the critical interface contained TNF-alpha and IL-1beta. These cytokines induced collagenase-3 secretion in cultured rheumatoid synovial fibroblasts. Procollagenase-3 activators, stromelysin-1, 72 kDa type IV collagenase/gelatinase and membrane-type 1-MMP, were also found in the pannus-hard tissue junction. Active collagenase-3 was inhibited with alendronate (IC50 = 500-750 microM). Collagenase-3, due to its substrate profile and local synthesis in a milieu favoring its activation, might play a major role in the degradation of cartilage type II and bone type I collagens. Alendronate, at concentrations attainable in vivo, is able to inhibit collagenase-3. This might offer an option to control collagenase-3-mediated tissue destruction in rheumatoid arthritis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0945-053X
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
401-12
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10517187-Adult, pubmed-meshheading:10517187-Aged, pubmed-meshheading:10517187-Alendronate, pubmed-meshheading:10517187-Arthritis, Rheumatoid, pubmed-meshheading:10517187-Blotting, Western, pubmed-meshheading:10517187-Cartilage, Articular, pubmed-meshheading:10517187-Collagenases, pubmed-meshheading:10517187-Enzyme Inhibitors, pubmed-meshheading:10517187-Exudates and Transudates, pubmed-meshheading:10517187-Female, pubmed-meshheading:10517187-Humans, pubmed-meshheading:10517187-Immunohistochemistry, pubmed-meshheading:10517187-Interleukin-1, pubmed-meshheading:10517187-Male, pubmed-meshheading:10517187-Matrix Metalloproteinase 13, pubmed-meshheading:10517187-Matrix Metalloproteinases, pubmed-meshheading:10517187-Middle Aged, pubmed-meshheading:10517187-Synovial Membrane, pubmed-meshheading:10517187-Tumor Necrosis Factor-alpha
pubmed:year
1999
pubmed:articleTitle
Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pannus-hard tissue junction and inhibition by alendronate.
pubmed:affiliation
Department of Medicine, Helsinki University Central Hospital, Finland. yrjo.konttinen@helsinki.fi
pubmed:publicationType
Journal Article