Role of matrix metalloproteinases and their tissue inhibitors in the pathological mechanisms underlying maxillofacial cystic lesions

Abstract

Cystic lesions are considered to be one of the most common pathologies of the maxillofacial region, and matrix metalloproteinases (MMPs) may represent potential etiological factors. The aim of the present study was to elucidate the role of MMP-2 and MMP-9, and their endogenous tissue inhibitors, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, respectively, in the pathogenesis of maxillofacial cystic lesions. A total of 25 patients diagnosed with radicular cysts (RCs; n=20), dentigerous cysts (n=3) and retention cysts (RtCs; n=7) were enrolled in the present study. Gelatin zymography was performed to assess the gelatinolytic activity of MMP-2 and MMP-9, and commercial ELISA kits were used to determine TIMP-1 and TIMP-2 concentrations. Gelatin zymography revealed the presence of both MMP-2 and MMP-9 in all types of samples analyzed. An increase in MMP-9 activity, TIMP-1 concentration and MMP-9/TIMP-1 ratio was observed in the fluid obtained from RCs compared with that obtained from RtCs. In conclusion, MMP-9 may be involved in the pathogenesis of RCs, whereas the activity of MMP-2 in the wall of RtCs was low, and this gelatinase did not appear to significantly affect the development of this type of lesion.

Keywords: dentigerous cyst; matrix metalloproteinase; matrixins; odontogenic cyst; radicular cyst; retentions cyst; tissue inhibitor of metalloproteinase; zymography.

Figure 1

Representative zymogram of the serum and cyst fluid from patients with RC, DC or RtC. S, serum; F, fluid; RC, radicular cyst; RtC, retention cyst; DC, dentigerous cyst; MMP, matrix metalloproteinase; NGAL, neutrophil gelatinase-associated lipocalin.

Figure 2

Representative zymogram of the cyst capsules of patients with RC, DC or RtC. RC, radicular cyst; RtC, retention cyst; DC, dentigerous cyst; MMP, matrix metalloproteinase.

Figure 3

Activity of MMP-9 in the cyst fluid from patients diagnosed with RC, DC or RtC. Statistically significantly higher activity of MMP-9 was observed in the RCs compared with the RtCs. ^*P=0.0065. OD, optical density; RC, radicular cyst; RtC, retention cyst; DC, dentigerous cyst; MMP, matrix metalloproteinase.

Figure 4

Activity of MMP-2 in the cyst capsules of patients diagnosed with RC, DC or RtC. The difference between RtC and DC were statistically significant. ^*P=0.046, Kruskal-Wallis; P<0.05, post hoc Dunns' test. OD, optical density; RC, radicular cyst; RtC, retention cyst; DC, dentigerous cyst; MMP, matrix metalloproteinase.

Figure 5

TIMP-1 serum levels in patients diagnosed with RC, DC or RtC. There were no significant differences in the levels of TIMP-1 between the different types of cysts. RC, radicular cyst; RtC, retention cyst; DC, dentigerous cyst; TIMP, tissue inhibitor of metalloproteinase.

Figure 6

MMP-9/TIMP-1 ratio in the cyst fluid of patients diagnosed with RC, DC or RtC. Comparison of the ratio in the MMP-9/TIMP-1 between RC and RtC trended towards statistical significance (P=0.09, Kruskal-Wallis test; ^#P<0.05, post hoc Dunns' test. OD, optical density; RC, radicular cyst; RtC, retention cyst; DC, dentigerous cyst; TIMP, tissue inhibitor of metalloproteinase; MMP, matrix metalloproteinase.