Biomedical Engineering Reference
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cells (as monocytes) is to stimulate MMP-9 expression by NFkB activation and
MAP-kinase signaling pathway. MMP-9 over-expression may impair normal
healing and cicatrization process [ 80, 104, 115, 118 ] .
TIMP-3 is one of the primary inhibitors for ADAM-17 and is involved in
inflammation regulation. While TIMP-3 is missing or secreted at low concentra-
tions, ADAM-17 activity is accentuated, inducing TNF alpha secretion and an
increase of the inflammatory fluid volume. Interaction between TIMP-3 and
ADAM-17 plays an important role in recruiting and redirecting leukocytes.
Vascular cell adhesion molecules (VCAM) are also involved in white blood
cells recruitment, and during inflammatory response they are cleaved at endothe-
lial cell surface by ADAM-17. TIMP-3 excess blocks soluble VCAM produc-
tion while the decreases of TIMP-3 levels are activating surface cleavage of
VCAM-1 [ 118 ] .
TIMP-1 may be involved in leukocyte flowing and vascular permeability by reg-
ulating apoptotic processes in endothelial cells. TIMP-1 plays an antiapoptotic
effect in endothelial cells. It appears that natural inhibitors for MMPs, mainly
TIMP-3, are required to adjust inflammatory cell response, by regulating cytokine
signaling and cell adhesion receptors.
TIMP also regulates some steps in cell migration. Epithelial cell migration
depends on TIMP-1 levels and is impaired by its low concentrations. There are
significant differences between epithelial and stromal cell migration during
re-epithelization and granulation tissue formation, while TIMP balance these pro-
cesses [ 34 ] .
2.10
Evaluation of Immunohistochemical Detection of MMPs
in Periimplant Tissues
Our group has performed various tests in order to detect the presence of some
MMPs (as gelatinases) in periimplant tissues. We have used simple immunohis-
tochemical detection of MMP-2 and -9, together with the detection of the TIMP-1
and -2, by using a DAB detection system bound to specific primary antibodies
against MMPs and TIMPs. For a semiquantitative evaluation of the immunohis-
tochemistry results, we have used the color deconvolution technique, imagined and
described by Ruifrok şi Johnston [ 101 ]. The analysis of our results showed that
MMP-9 is present in various amounts (expressed in area percentage on the exam-
ined slides) of 33,010, 27,878, 15,857, 30,213, and 31,852 %, compared to the
normal witness slide (without implant) where the MMP-9 marked area was of
9,614 % only. Thus, MMP appear to be involved in ECM remodeling processes in
the peri-implant area. TIMP-1 expression is also increased in the peri-implant area,
showing that remodeling processes require the presence of the enzyme and its nat-
ural inhibitor at the same time.
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