Membrane-type I matrix metalloproteinase-dependent regulation of rheumatoid arthritis synoviocyte function.
J Immunol
; 184(11): 6396-406, 2010 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-20483788
ABSTRACT
In rheumatoid arthritis, the coordinated expansion of the synoviocyte mass is coupled with a pathologic angiogenic response that leads to the destructive remodeling of articular as well as surrounding connective tissues. Although rheumatoid synoviocytes express a multiplicity of proteolytic enzymes, the primary effectors of cartilage, ligament, and tendon damage remain undefined. Herein, we demonstrate that human rheumatoid synoviocytes mobilize the membrane-anchored matrix metalloproteinase (MMP), membrane-type I MMP (MT1-MMP), to dissolve and invade type I and type II collagen-rich tissues. Though rheumatoid synoviocytes also express a series of secreted collagenases, these proteinases are ineffective in mediating collagenolytic activity in the presence of physiologic concentrations of plasma- or synovial fluid-derived antiproteinases. Furthermore, MT1-MMP not only directs the tissue-destructive properties of rheumatoid synoviocytes but also controls synoviocyte-initiated angiogenic responses in vivo. Together, these findings identify MT1-MMP as a master regulator of the pathologic extracellular matrix remodeling that characterizes rheumatoid arthritis as well as the coupled angiogenic response that maintains the aggressive phenotype of the advancing pannus.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Membrana Sinovial
/
Metaloproteinase 14 da Matriz
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos