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MR Vol.10 No.3 indexに戻る
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MODERN RHEUMATOLOGY
Vol.10 No.3 |
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Matrix-degrading metalloproteinases and
their roles in joint destruction |
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| Y. Okada1 |
| (1)Department of Pathology, School of Medicine,
Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan |
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| Abstract |
| Abstract Progressive degradation of the extracellular
matrix (ECM) of articular cartilage and bone by enhanced activities
of proteinases is an essential step for joint destruction in rheumatoid
arthritis (RA) and osteoarthritis (OA). Among the proteinases,
matrix-degrading metalloproteinases play a key role in joint destruction.
Recent studies have indicated that these metalloproteinases comprise
members of the matrix metalloproteinase (MMP) and a disintegrin
and metalloproteinase (ADAM) gene families. The MMP family is composed
of 19 different members and classified into five subgroups of collagenases,
gelatinases, stromelysins, membrane-type MMPs, and other MMPs.
They have the ability to digest almost all ECM components in human
tissues when they act in concert. Their prospective roles in RA
and OA joint destruction have been well established. On the other
hand, the ADAM family members are classified into ADAM metalloproteinases
and catalytically inactive nonproteolytic homologues. The ADAM
metalloproteinases contain ADAM with a transmembrane domain (membrane-type
ADAM) and ADAM with thrombospondin motifs (ADAMTS). Although members
in both groups are known to degrade ECM components, ADAMTS species
may be especially important for the aggrecan (cartilage proteoglycan)
degradation of articular cartilage in RA and OA, since aggrecanases-1
and -2 are included in this group. This review outlines the characters
of the MMP and ADAM gene family members and their roles in joint
destruction in RA and OA. |
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| Key words |
| Key words Rheumatoid arthritis ・ Osteoarthritis
・ Matrix metalloproteinase ・ A disintegrin and metalloproteinase
・ Joint destruction ・ Matrix
degradation |
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