title: High matrix metalloproteinase activity is a hallmark of periapical granulomas.
abstract: BACKGROUND
  The inability to distinguish periapical cysts from granulomas before 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. Because 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 by using one-way analysis of variance followed by the Tukey test.
  
  
  RESULTS
  We observed that cysts and granulomas differentially expressed several ECM molecules, especially those from the MMP family. Compared with 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 with cysts.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
authors.forename: Francisco Wanderley Garcia
authors.initials: FW
authors.lastname: de Paula-Silva
authors.forename: Nisha J
authors.initials: NJ
authors.lastname: D'Silva
authors.forename: Léa Assed Bezerra
authors.initials: LA
authors.lastname: da Silva
authors.forename: Yvonne Lorraine
authors.initials: YL
authors.lastname: Kapila
mesh_terms: D016022:Case-Control Studies; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009504:Neutrophils / Q000201:enzymology; D020411:Oligonucleotide Array Sequence Analysis; D010484:Periapical Granuloma / Q000175:diagnosis / Q000201:enzymology*; D010513:Periodontal Ligament / Q000201:enzymology; D011842:Radicular Cyst / Q000175:diagnosis / Q000201:enzymology
chemical_list: D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9