High Matrix Metalloproteinase Activity Is a Hallmark of Periapical Granulomas

Abstract

Introduction Inability to distinguish periapical cysts from granulomas prior to performing root canal treatment leads to uncertainty in treatment outcomes, because cysts have lower healing rates. Searching for differential expression of molecules within cysts or granulomas could provide information with regard to the identity of the lesion or suggest mechanistic differences that may form the basis for future therapeutic intervention. Thus, we investigated whether granulomas and cysts exhibit differential expression of extracellular matrix (ECM) molecules. Methods Human periapical granulomas, periapical cysts, and healthy periodontal ligament tissues were used to investigate the differential expression of ECM molecules by microarray analysis. Since matrix metalloproteinases (MMP) showed the highest differential expression in the microarray analysis, MMPs were further examined by in situ zymography and immunohistochemistry. Data were analyzed using one-way ANOVA followed by Tukey test. Results We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the matrix metalloproteinase (MMP) family. Compared to cysts, granulomas exhibited higher MMP enzymatic activity in areas stained for MMP-9. These areas were composed of polymorphonuclear cells (PMNs), in contrast to cysts. Similarly, MMP-13 was expressed by a greater number of cells in granulomas compared to cysts. Conclusion Our findings indicate that high enzymatic MMP activity in PMNs together with MMP-9 and MMP-13 stained cells could be a molecular signature of granulomas, unlike periapical cysts.

Bioinformatics, Interaction Network Analysis, and Neural Networks to Characterize Gene Expression of Radicular Cyst and Periapical Granuloma

“…Some studies suggested that regulatory inflammatory proteins such as FOXP3, GATA3, and IL10 have increased in PGs in comparison with RCs (4,18,51). It was shown that FOXP3/GATA3 double-positive cells only suppress non-TH2 cytokines and might contribute to the Basic Research-Biology polarization, amplification, or both of the allergen-specific TH2 response in sensitized subjects instead of controlling it (52).…”

Cysteine Cathepsins in Human Dentin-Pulp Complex

“…MMPs might be involved in several physiologic processes in dentin-pulp complex, including the organization of matrix before mineralization, control of mineralization, peritubular dentin formation, and matrix alterations during aging (5,7,14,20). MMPs have also been identified in both pulpal and periapical inflammation (21)(22)(23)(24), and they are involved in dentin matrix destruction in caries (25)(26)(27). Dental adhesives are capable of activating dentin-bound MMPs in coronal (15,28) and radicular (29) dentin.…”

Midkine Expression in Human Periapical Granulomas

“…Our results showed that MK was significantly expressed in periapical granulomas and could be important in immune response around periapical areas. On the other hand, de Paula-Silva et al (22) analyzed matrix metalloproteinase activity in periapical granulomas and radicular cysts and showed that high matrix metalloproteinase activity could be a molecular signature of periapical granulomas. Therefore, additional studies of MK expression in periapical granulomas and radicular cysts could be useful to find the profiles of periapical lesions.…”