Expression and Significance of Mucin-4 and Matrix Metalloproteinase-7 in Peri-implant Disease

Overview

Journal Hua Xi Kou Qiang Yi Xue Za Zhi

Specialty Dentistry

Date 2024 Apr 10

PMID 38596992

Authors

Dandan Jiang

Zheng Zhou

Yufeng Shen

Xiaoxue Tang

Xiaorui Gou

Meiyu Huang

Yizhou Tong

Miaomiao Chen

Chong-Qing Yu

Affiliations

Soon will be listed here.

Abstract

Objectives: This study aims to detect the levels of mucin (MUC)-4, metalloproteinase (MMP)-7, and MMP-8 in peri-implant crevicular fluid (PICF) and investigate whether the novel combinations of MMP-7 and MUC-4 are effective markers of peri-implant diseases, particularly when used in the PICF of healthy individuals, to provide a theoretical basis for finding a novel reference index that can aid the diagnosis, evaluation, and treatment of peri-implant diseases.

Methods: A total of 63 subjects with 2-5 years of upper prosthesis loading were selected according to inclusion and exclusion criteria, composed of 24 controls and 39 patients with peri-implantitis (PI) group. MUC-4, MMP-7, and MMP-8 levels were detected through enzyme linked immunosorbent assay (ELISA).

Results: No significant differences in age, sex, and other parameters were found between the PI and control groups. The PI group had higher MMP-7 and MMP-8 expression levels (<0.05) but lower MUC-4 level (<0.001). Correlation analysis showed that MMP-7 was positively correlated with pocket probing depth (PPD) (=0.451, <0.001); MMP-8 was positively correlated with PPD, bleeding on probing (BOP), and gingival index (GI) (=0.619, <0.001; =0.478, <0.001; =0.332, =0.009). MUC-4 was negatively correlated with PPD, BOP, and GI (=-0.492, <0.001; =-0.321, =0.010; =-0.396, =0.001). MMP-7, MMP-8, and MUC-4 had certain diagnostic efficacy for PI. MMP-8 exhibited the best diagnostic efficacy for PI. When the cutoff value of MMP-8 was >21.21, the area under the curve (AUC) was 0.868, and the sensitivity and specificity for the diagnosis of PI were 0.96 and 0.68, respectively. The diagnostic efficacy of MMP-7 and MUC-4 parallel diagnostic models was higher than that of each factor, and the diagnostic sensitivity of the model for PI was 0.96, and the specificity was 0.56.

Conclusions: Differences in MMP-7 and MUC-4 levels were found between the inflammation and control groups and may be diagnostic indicators for predicting PI; combinations of MMP-7 and MUC-4 had a good diagnostic value for inflammation.

References

Salvi G, Cosgarea R, Sculean A . Prevalence and Mechanisms of Peri-implant Diseases. J Dent Res. 2016; 96(1):31-37. DOI: 10.1177/0022034516667484. View

Emingil G, Tervahartiala T, Mantyla P, Maatta M, Sorsa T, Atilla G . Gingival crevicular fluid matrix metalloproteinase (MMP)-7, extracellular MMP inducer, and tissue inhibitor of MMP-1 levels in periodontal disease. J Periodontol. 2007; 77(12):2040-50. DOI: 10.1902/jop.2006.060144. View

Kiili M, Cox S, Chen H, Wahlgren J, Maisi P, Eley B . Collagenase-2 (MMP-8) and collagenase-3 (MMP-13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue. J Clin Periodontol. 2002; 29(3):224-32. DOI: 10.1034/j.1600-051x.2002.290308.x. View

Schwarz F, Derks J, Monje A, Wang H . Peri-implantitis. J Periodontol. 2018; 89 Suppl 1:S267-S290. DOI: 10.1002/JPER.16-0350. View

Serino G, Turri A, Lang N . Probing at implants with peri-implantitis and its relation to clinical peri-implant bone loss. Clin Oral Implants Res. 2012; 24(1):91-5. DOI: 10.1111/j.1600-0501.2012.02470.x. View

Sorsa T, Gieselmann D, Arweiler N, Hernandez M . A quantitative point-of-care test for periodontal and dental peri-implant diseases. Nat Rev Dis Primers. 2017; 3:17069. DOI: 10.1038/nrdp.2017.69. View

Lundmark A, Johannsen G, Eriksson K, Kats A, Jansson L, Tervahartiala T . Mucin 4 and matrix metalloproteinase 7 as novel salivary biomarkers for periodontitis. J Clin Periodontol. 2016; 44(3):247-254. PMC: 5347886. DOI: 10.1111/jcpe.12670. View

Nobrega F, Oliveira D, Vasconcelos R, Nonaka C, Guedes Queiroz L . Study of the participation of MMP-7, EMMPRIN and cyclophilin A in the pathogenesis of periodontal disease. Arch Oral Biol. 2016; 72:172-178. DOI: 10.1016/j.archoralbio.2016.08.032. View

Renvert S, Persson G, Pirih F, Camargo P . Peri-implant health, peri-implant mucositis, and peri-implantitis: Case definitions and diagnostic considerations. J Periodontol. 2018; 89 Suppl 1:S304-S312. DOI: 10.1002/JPER.17-0588. View

10.

Almehmadi A, AlGhamdi F . Biomarkers of alveolar bone resorption in gingival crevicular fluid: A systematic review. Arch Oral Biol. 2018; 93:12-21. DOI: 10.1016/j.archoralbio.2018.05.004. View

11.

Leeman M, Curran S, Murray G . New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression. J Pathol. 2003; 201(4):528-34. DOI: 10.1002/path.1466. View

12.

Fu X, Kassim S, Parks W, Heinecke J . Hypochlorous acid oxygenates the cysteine switch domain of pro-matrilysin (MMP-7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rupture by myeloperoxidase. J Biol Chem. 2001; 276(44):41279-87. DOI: 10.1074/jbc.M106958200. View

13.

Uitto V, Salonen J, Firth J, Jousimies-Somer H, Saarialho-Kere U . Matrilysin (matrix metalloproteinase-7) expression in human junctional epithelium. J Dent Res. 2002; 81(4):241-6. DOI: 10.1177/154405910208100404. View

14.

Alfakry H, Malle E, Koyani C, Pussinen P, Sorsa T . Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease. Innate Immun. 2015; 22(1):85-99. DOI: 10.1177/1753425915617521. View

15.

Sanchez G, Miozza V, Delgado A, Busch L . Determination of salivary levels of mucin and amylase in chronic periodontitis patients. J Periodontal Res. 2010; 46(2):221-7. DOI: 10.1111/j.1600-0765.2010.01332.x. View

16.

. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001; 69(3):89-95. DOI: 10.1067/mcp.2001.113989. View

17.

Ho B, Wu Y, Chang K, Pan T . Dimerumic acid inhibits SW620 cell invasion by attenuating H₂O₂-mediated MMP-7 expression via JNK/C-Jun and ERK/C-Fos activation in an AP-1-dependent manner. Int J Biol Sci. 2011; 7(6):869-80. PMC: 3149281. DOI: 10.7150/ijbs.7.869. View

18.

Belibasakis G, Bostanci N, Marsh P, Zaura E . Applications of the oral microbiome in personalized dentistry. Arch Oral Biol. 2019; 104:7-12. DOI: 10.1016/j.archoralbio.2019.05.023. View

19.

Hallstrom H, Persson G, Lindgren S, Olofsson M, Renvert S . Systemic antibiotics and debridement of peri-implant mucositis. A randomized clinical trial. J Clin Periodontol. 2012; 39(6):574-81. DOI: 10.1111/j.1600-051X.2012.01884.x. View

20.

Bhavsar I, Miller C, Ebersole J, Dawson 3rd D, Thompson K, Al-Sabbagh M . Biological response to peri-implantitis treatment. J Periodontal Res. 2019; 54(6):720-728. DOI: 10.1111/jre.12681. View