Publication: Interleukin-1ß-induced expression of the urokinase-type plasminogen activator receptor and its co-localization
with MMPs in human articular chondrocytes
Authors
Schwab, W. ; Schulze-Tanzil, G. ; Mobasheri, A. ; Dressler, J. ; Kotzsch, M. ; Shakibaei, M.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The urokinase-type plasminogen activator
receptor (uPAR) plays a critical role in cartilage
degradation during osteoarthritis as it regulates
pericellular proteolysis mediated by serine proteinases.
Another important family of proteinases responsible for
ECM destruction in arthritis are the matrix
metalloproteinases (MMPs). MMPs are regulated by IL-
1ß, a cytokine that plays a pivotal role in pathogenesis of
osteoarthritis. This study was undertaken to address two
questions: 1. Is uPAR-expression regulated by
proinflammatory cytokines such as IL-1ß? 2. Does a
functional co-localization exist between uPAR and
MMPs?
By immunohistochemical analysis we observed
enhanced expression of uPAR on chondrocytes derived
from osteoarthritic human cartilage compared to nonosteoarthritic
controls. We found an IL-1ß-mediated
expression of uPAR by immunoelectron microscopy.
Western blot analysis demonstrated that IL-1ßstimulated
expression of uPAR on chondrocytes in vitro
increased in a dose-dependent manner. Furthermore, we
found a functional co-localization between uPAR and
MMP-9 on IL-1ß-stimulated chondrocytes by means of a
co-immunoprecipitation assay.
Expression of uPAR in osteoarthritic cartilage but
not in healthy cartilage suggests that uPAR plays a role
in cartilage breakdown. We propose that uPAR-mediated
effects e.g. pericellular proteolysis are one of other
cytokine (IL-1ß)-mediated events that contribute to the
pathogenesis of osteoarthritis. Furthermore, we found
that MMPs and uPAR were part of the same cell surface
complexes in chondrocytes. This finding underlines a
functional interaction between MMPs and the serine
proteinase system in the fine regulation of pericellular
proteolysis. Interfering with uPAR signaling may present
a novel target in arthritis therapy to prevent excessive proteolytic degradation.
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