Background: The plasminogen activator system has been proposed to play a ro
le in proteolytic degradation of extracellular matrices in tissue remodelin
g, including wound healing. The aim of this study was to elucidate the pres
ence of components of the plasminogen activator system during different sta
ges of periodontal wound healing.
Methods: Periodontal wounds were created around the molars of adult rats an
d healing was followed for 28 days. Immunohistochemical analyses of the hea
ling tissues and an analysis of the periodontal wound healing fluid by ELIS
A were carried out for the detection of tissue-type plasminogen activator (
t-PA), urokinase-type plasminogen activator (u-PA), and 2 plasminogen activ
ator inhibitors (PAI-1 and PAI-2).
Results: During the early stages (days 1 to 3) of periodontal wound healing
, PAI-1 and PAI-2 were found to be closely associated with the deposition o
f a fibrin clot in the gingival sulcus. These components were strongly asso
ciated with the infiltrating inflammatory cells around the fibrin clot. Dur
ing days 3 to 7, u-PA, PAI-1, and PAI-2 were associated with cells (particu
larly monocytes/macrophages, fibroblasts, and endothelial cells) in the new
ly formed granulation tissue. During days 7 to 14, a new attachment apparat
us was formed during which PAI-1, PAI-2, and u-PA were localized in both pe
riodontal ligament fibroblasts (PDL) and epithelial cells at sites where th
ese cells were attaching to the root surface. In the periodontal wound heal
ing fluid, the concentration for t-PA increased and peaked during the first
week. PAI-2 had a similar expression to t-PA, but at a lower level over th
e entire wound-healing period.
Conclusions: These findings indicate that the plasminogen activator system
is involved in the entire process of periodontal wound healing, in particul
ar with the formation of fibrin matrix on the root surface and its replacem
ent by granulation tissue, as well as the subsequent formation of the attac
hment of soft tissue to the root surface during the later stages of wound r
epair.