Background: Tissue destruction associated with the progression of periodontal disease is caused by a cascade of host and microbial proteolytic enzymes. Host-derived matrix metalloproteinases (MMPs) play an important role in the degradation of the extracellular matrix. Leukolysin/membrane-type 6 (MT-6)/MMP-25, the latest member of the MT-MMP subgroup of the MMP family, is primarily expressed by neutrophils and involved in extracellular matrix turnover. Matrilysin-2/MMP-26 (endometase), a novel member of the matrilysin subgroup of the MMP family, can degrade the extracellular matrix, alpha1-antitrypsin, and activate pro-MMP-9. Our study aimed to examine the levels, molecular forms, and degrees of activation of MMP-25 and MMP-26 in gingival crevicular fluid (GCF) from patients with different periodontal diseases.
Methods: A total of 105 subjects, 35 with generalized aggressive periodontitis (GAgP), 29 with chronic periodontitis (CP), 20 with gingivitis, and 21 periodontally healthy subjects, were included in this study. Periodontal status was evaluated by measuring probing depth, clinical attachment loss, presence of bleeding on probing, and plaque. GCF MMP-25 and MMP-26 levels were analyzed by computer-quantitated Western immunoblotting using specific antibodies.
Results: The 57-kDa soluble pro-MMP-25 and 45- to 47-kDa active form of MMP-25 were detected by Western immunoblots in CP and GAgP GCF, and lesser levels of these soluble MMP-25 immunoreactive bands were detected in gingivitis GCF. An enhanced and similar degree of MMP-25 activation was found in GAgP, CP, and gingivitis groups. There were no detectable MMP-25 immunoreactivities in the healthy subjects' GCF. GAgP and CP groups had elevated GCF MMP-26 levels and degrees of activation compared to the gingivitis and healthy groups (P <0.008). The gingivitis group had higher GCF MMP-26 levels and degree of activation compared to the healthy group (P <0.008).
Conclusions: The present study demonstrated the presence of soluble or shed forms of MMP-25 and MMP-26 in GCF of patients with different periodontal diseases. Increased levels and activation of MMP-25 and MMP-26 in GCF are associated with an enhanced severity of periodontal inflammation, suggesting that these novel MMPs can participate in the progression of periodontal diseases. They may prove to be diagnostically useful and could be targets of medication in the future.