Periodontal disease and gene-expression levels of metalloendopeptidases in human buccal mucosal epithelium.
OBJECTIVE
Endopeptidases, such as neutral endopeptidase (NEP), endothelin-converting enzyme-1 (ECE-1) and a disintegrin and metalloprotease 17 (ADAM17), are believed to have various important roles in oral mucosal and epidermal tissue for the regulation of defensive biological responses in the oral cavity, and their expression and activity are influenced by various factors, including oral diseases. However, knowledge concerning these endopeptidases in the oral cavity has been minimal until now. This study focused on three metalloendopeptidases - NEP, ECE-1 and ADAM17 - in the oral buccal mucosal epithelium of patients with periodontal diseases and investigated the relationship between their gene-expression levels and periodontal disease.


METHODS
The levels of expression of NEP, ECE-1 and ADAM17 mRNAs in tissue samples collected from the oral buccal mucosal epithelium of 61 patients were investigated by relative quantification using real-time RT-PCR analysis. information on oral and systemic health was obtained from the clinical record of each patient.


RESULTS
Among the three groups, classified based on the diagnosis of periodontal diseases (healthy/gingivitis, early periodontitis and moderate/advanced periodontitis), the relative expression level of NEP mRNA was significantly increased in the early periodontitis group and in the moderate/advanced periodontitis group compared with that in the healthy/gingivitis group. Moreover, the relative expression levels of ECE1 and ADAM17 mRNAs were significantly increased in the moderate/advanced periodontitis group compared with those in the healthy/gingivitis group. The correlation coefficients between the mean relative expression levels of NEP and ECE1 mRNAs, NEP and ADAM17 mRNAs, and ECE1 and ADAM17 mRNAs were r = 0.758, r = 0.707 and r = 0.934, respectively (p < 0.001). Furthermore, among the oral-related factors, there was a significant correlation between the number of sites with probing pocket depths of more than 4 mm and of more than 6 mm and the relative expression levels of NEP, ECE1 and ADAM17 mRNAs. In stepwise logistic regression models, high relative expression levels of ECE1 and ADAM17 mRNAs were significantly associated with moderate/advanced periodontitis.


CONCLUSIONS
The present study suggests that the severity of periodontal disease may be associated with the expression of metalloendopeptidase genes, including NEP, ECE1 and ADAM17, in the buccal mucosal epithelium.
Division of Community Oral Health Science, Department of Health Promotion, Kyushu Dental College, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, 803-8580, Japan.
N
N
Kinoshita
S
S
Awano
A
A
Yoshida
I
I
Soh
T
T
Ansai
D051722:ADAM Proteins / Q000235:genetics; D000072198:ADAM17 Protein; D000368:Aged; D016301:Alveolar Bone Loss / Q000201:enzymology / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D055113:Chronic Periodontitis / Q000201:enzymology / Q000235:genetics; D000072396:Endothelin-Converting Enzymes; D004848:Epithelium / Q000201:enzymology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005884:Gingival Hemorrhage / Q000201:enzymology / Q000235:genetics; D005891:Gingivitis / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology*; D015260:Neprilysin / Q000235:genetics; D010514:Periodontal Pocket / Q000201:enzymology / Q000235:genetics; D010518:Periodontitis / Q000201:enzymology* / Q000235:genetics; D010519:Periodontium / Q000201:enzymology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
D014409:Tumor Necrosis Factor-alpha; D016282:Aspartic Acid Endopeptidases; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D015260:Neprilysin; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human
a disintegrin and metalloprotease 17; endothelin-converting enzyme-1; neutral endopeptidase; periodontal disease