Roles of metalloproteinase-3 and aggrecanase
1 and 2 in aggrecan cleavage during human meniscus degeneration.
ADAMTS1, -4, -5, -8, -9 and -15 have aggrecanase
activity whereas other members do not.
Cloning and characterization of ADAMTS11, an aggrecanase
from the ADAMTS family.
from Wyeth Pharmaceuticals outlined an unpublished study showing that in preclinical animal models aggrecanase
activ ity is significantly increased immediately following injury, suggesting the potential for postsurgery aggrecanase
inhibition "'to stop/slow down not only immediate cartilage degradation but also development of cartilage destruction in later years.
n-3 dose-dependently decreased the IL1-induced aggrecanase
activity and basal aggrecanase
and collagenase activity, whereas, in contrast, n-6 stimulated the basal aggrecanase
and collagenase activity (74-77).
ADAMTS5 is the major aggrecanase
in mouse cartilage in vivo and in vitro.
5) The inhibition of aggrecanase
response was reported to be a consequence of metabolic changes that followed a marked increase in the intracellular glucosamine concentration, the exact mechanisms not yet being fully elucidated.
When stimulated there is an increase in cell expression in the chondrocytes of several matrix metalloproteinases (MMPs) such as MMP 1, 3 and 13, and prostaglandin E-2 (PGE-2), and aggrecanases
such as a disintegrin and metalloproteinase with thrombospondin motif 4 (ADAMTS-4).
Hughes, "The role of synovial macrophages and macrophage-produced cytokines in driving aggrecanases
, matrix metalloproteinases, and other destructive and inflammatory responses in osteoarthritis," Arthritis Research and Therapy, vol.
Relative messenger RNA expression profiling of collagenases and aggrecanases
in human articular chondrocytes in vivo and in vitro.
They discovered that these agents decreased interleukin-1-induced gene expression of several matrix metalloproteinases and aggrecanases
involved in cartilage breakdown.
These include not only the production of metalloproteinases, collagenases, and aggrecanases
that lead to cartilage breakdown in chondrocytes, but also the production of cytokines, such as interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, and nitric oxide (NO).