Matrix metalloproteinase-8 expression in periodontal tissues surgically removed from diabetic and non-diabetic patients with periodontal disease.

Patients with either type 1 or type 2 diabetes have increased prevalence and severity of periodontal disease when compared with nondiabetic subjects (Mealey, 1999). Thus, periodontal disease has been considered as another diabetic complication besides cardiovascular disease, nephropathy, retinopathy, neuropathy and peripheral vascular diseases (Grossi and Genco, 1998). Although earlier studies proposed that altered immune response, impaired host defense and increased susceptibility to infection in diabetic patients were the underlying mechanisms for greater risk for periodontal disease in diabetic patients (Mealey, 1999), increasing evidence in recent years has indicated a crucial role of pathogen-triggered inflammatory response from host in the pathogenesis of diabetes-associated periodontal disease (Salvi et al., 2005, Salvi et al., 1998, Nishimura et al., 2007, Genco et al., 2005). It has been shown that diabetic patients with periodontal disease have significantly higher levels of inflammatory mediators such as interleukin-1 (IL-1)β, tumor necrosis factor (TNF)α, and prostaglandin E2 (PGE2) in the gingival crevicular fluid (GCF) as compared to nondiabetic patients, and mononuclear phagocytes isolated from diabetic patients have exaggerated inflammatory responses to lipopolysaccharide (LPS) (Salvi et al., 1998). The studies from our group also showed that periodontal IL-6 mRNA and protein levels increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone, and patients with both diseases (Cole et al., 2008, Ross et al., 2010). In supporting these findings from patient studies, our in vitro studies have shown that high glucose in culture medium increased proinflammatory cytokine production by mononuclear cells in response to LPS (Maldonado et al., 2004). Both LPS and proinflammatory cytokines such as IL-6, IL-1β and TNFα are potent stimulators for matrix metalloproteinase (MMP) expression by mononuclear cells (Li et al., 2010). MMPs belong to a family of zinc-dependent endopeptidases and are capable of degrading collagen and other matrix proteins in connective tissue (Davidson et al., 2002). Numerous studies have shown that elevated levels of MMPs, especially MMP-8 (neutrophil collagenase), in GCF, saliva and mouth rinse samples are associated with the progression of periodontal disease (Mancini et al., 1999, Uitto et al., 2003, Sorsa et al., 2004, Leppilahti et al., Lee et al., 1995, Mantyla et al., 2006, Mantyla et al., 2003). Although the pathological role of MMP-8 in periodontal disease is well known, the information regarding the relationship between periodontal MMP-8 expression and diabetes remains controversial. By analysis of MMP-9 expression in gingival tissue using Western blot and gelatin zymography, Kumar et al. reported that MMP-8 level was increased by 2 folds in chronic periodontitis patients with diabetes compared to chronic periodontitis patients without diabetes (Kumar et al., 2006). Collin et al. also reported that advanced periodontitis in type 2 diabetes was related to elevated salivary MMP-8 levels (Collin et al., 2000). However, a recent study by Buduneli and coworkers showed that diabetes did not significantly affect GCF levels of MMP-8 (Kardesler et al., 2010). Costa et al. also reported that salivary MMP-9 concentrations were elevated regardless of periodontal inflammation in patients with diabetes (Costa et al., 2010). Thus, more investigations are necessary to determine if the state of diabetes in patients with periodontal disease is associated with increased periodontal MMP-8 expression. In this study, we recruited 32 patients with or without periodontal disease and diabetes and collected periodontal tissue specimens at the time of necessary surgical intervention and analyzed periodontal MMP-8 protein levels using immunohistochemistry. Results showed that periodontal MMP-8 expression is significantly increased across patients with neither periodontal disease nor diabetes, patients with periodontal disease alone, and patients with both diseases.