Accuracy of Gingival Crevicular Fluid Biomarkers of MMP8, TIMP1, RANK, RANKL, and OPG in Differentiating Symptomatic and Asymptomatic Apical Periodontitis

Abstract

Apical periodontitis (AP) is the most prevalent chronic inflammatory disease of the teeth. Bone resorption dynamics in symptomatic and asymptomatic AP are still unrecognized. This study examined different inflammatory markers within gingival crevicular fluid, including matrix metalloproteinases 8 (MMP8), tissue inhibitors of metalloproteinases 1 (TIMP1), receptor activator of nuclear factor κB (RANK), its ligand (RANKL), and osteoprotegerin (OPG), to be used in comparing symptomatic apical periodontitis (SAP) and asymptomatic apical periodontitis (AAP) versus healthy teeth. Subjects with SAP, AAP, and a control group were recruited and GCF samples were collected by Periopaper strips. Clinical and radiographical measures were used for diagnosing AP. Levels of MMP8, TIMP, RANK, RANKL, and OPG were determined by ELISA and their abilities to discriminate between examined sites were evaluated by receiver operator characteristic (ROC) curves. All examined biomarkers were statistically significant higher (p < 0.05) in SAP than AAP and the control group, apart from RANK. Significant positive correlations (p < 0.05) were identified between all SAP and AAP biomarkers except TIMP1 and RANK in AAP teeth. TIMP1 and OPG exhibited the highest ability to distinguish between SAP and AAP with areas under the curve of 0.824 and 0.763 in comparing SAP and the control group, and 0.732 and 0.73 when comparing AAP and the control group, respectively. Additionally, TIMP1 and OPG showed the highest AUC of 0.778 and 0.747 when SAP and AAP were compared, respectively. This study concluded that GCF levels of TIMP1 and OPG can be used to differentiate between SAP, AAP, and healthy teeth.

Keywords: GCF; accuracy; apical periodontitis; biomarkers; endodontic.

Figure 1

Flow diagram of the study.

Figure 2

Radiographical CBCT images of cases included in this study: (A) tooth #5 with AAP, (B) another case tooth #5 with SAP.

Figure 3

Intra-crevicular collection of GCF.

Figure 4

Shows the comparison of biomarkers level among all examined sites: (A) the level of MMP8 ng/mL; (B) the level of TIMP1 ng/mL; (C) the level of RANK ng/mL; (D) the level of RANKL ng/mL; (E) the level of OPG ng/mL; and (F) the level of GCF volume; * p < 0.05; ** p < 0.01.

Figure 5

ROC curves for examined GCF biomarkers to differentiate between SAP and the control group (A), AAP and the control group (B), and SAP and AAP (C).