Exploration Of The Relationship Between MMP-7,MUC-4 And Peri-implant Disease

Objective: 1.To detect the expression levels of MMP-8,MMP-7 and MUC-4 in peri-implant crevicular fluid(PICF)of peri-implant inflammatory and healthy samples;2.To analyze the relationship between MMP-8,MMP-7,MUC-4 levels and peri-implant clinical parameters;3.To preliminarily investigate whether the novel marker combinations MMP-7 and MUC-4 have the ability to distinguish peri-implant diseases individuals from healthy individuals in PICF,in order to provide a theoretical basis for finding novel indicators to assist in the diagnosis,evaluation and treatment of periimplant diseases.Methods: 63 subjects(63 implants)were selected according to the inclusion and exclusion criteria,from the patients who visited the Department of Stomatology of the First Affiliated Hospital of Shihezi University School of Medicine from July 2014 to July 2019,including 24 subjects in the peri-implantitis group(PI group)and 39 subjects in the control group.All subjects received implant-restored posterior teeth and loaded for 2-5 years.General and clinical information such as age,gender,and past history were collected from each subject,and if there were multiple implants in the oral,the subjects in the PI group were selected as the implant with the worst clinical condition,and the subjects in the control group were selected as the implant which is the most accessible.Pocket probing depth(PPD),bleeding index(BOP),gingival index(GI),and modified plaque index(m PLI)were collected from each implant;Reexamination cone-beam CT films were taken to obtain bone resorption parameters by comparing with the first radiography taken after implantation(original films);supragingival plaque on the implant neck was removed and moisture-barrier was performed to obtain PICF at 6 sites(mesio-buccal,mesio-lingual,disto-buccal,disto-lingual,centralbuccal,central-lingual)from each implant,and the supernatant was taken and cryopreserved after centrifugation.Matrix metalloproteinase-7(MMP-7),mucin-4(MUC-4),and matrix metalloproteinase-8(MMP-8)levels in the PICF of the two groups of subjects were obtained by enzyme-linked immunosorbent assay(ELISA).The differences of the collected indicators in the two groups were statistically analyzed.Spearman correlation test was used to assess the correlation between MMP-7,MUC-4,MMP-8 indicators and periodontal probing indexes.Binary logistic regression was used to analyze the influencing factors of implant inflammation.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve was used to evaluate diagnostic efficacy of MMP-7,MMP-8,MUC-4 for peri-implantitis.The test level which was α = 0.05 and P < 0.05 considered statistically significant.Result: 1.There were no significant differences in age,sex and other parameters between PI group and control group.The expression levels of MMP-7 and MMP-8 in the PI group were higher than those in the control group(P < 0.05),and the MUC-4 levels in the PI group were lower than those in the control group(P < 0.001).2.A risk prediction model for PI was constructed using MMP-7,MMP-8,and MUC-4 indicators as independent variables,and the results showed that PI was positively correlated with the level of MMP-8(OR = 1.121),negatively correlated with the level of MUC-4(OR = 0.670),and not statistically significantly correlated with the level of MMP-7(OR = 1.057).3.Correlation analysis showed that MMP-7 was positively correlated with PPD(r = 0.451,P < 0.001);MMP-8 was positively correlated with PPD,BOP and GI(r = 0.619,0.478,0.332,P < 0.01);MUC-4 was negatively correlated with PPD,BOP and GI(r =-0.492,-0.321,-0.396,P < 0.05);4.MMP-7,MMP-8 and MUC-4 have diagnostic efficacy for PI.When the cut-off values of MMP-7,MMP-8 and MUC-4 are 21.56,21.21 and 4.58,respectively.MMP-8 has the best diagnostic efficacy for PI.When the cut-off value of MMP-8 > 21.27,the area under the curve is 0.868,the sensitivity and specificity for the diagnosis of PI are 0.9583 and 0.6757,respectively.The diagnostic efficacy of MMP-7 and MUC-4 parallel diagnostic models was higher than that of the two factors alone,and the diagnostic sensitivity of the model for PI was 0.958 and the specificity was 0.564.Conclusion: 1.The levels of MMP-8,MMP-7 and MUC-4 are different between PI and control group,which may be a diagnostic indicators for predicting the presence of PI;2.There are some correlations between MMP-8,MMP-7,MUC-4 in PICF and some clinical indexes,suggesting that the changes of MMP-7,MMP-8 and MUC-4 contents are related to the degree of inflammation in the soft and hard tissues around the implants,which may be become reference indexes to monitor the occurrence and development of the disease.