Active Matrix Metalloproteinase-8: Contributor to Periodontitis and a Missing Link Between Genetics, Dentistry, and Medicine

Abstract

Periodontitis is one of the most common infection-induced inflammatory tissue destructive diseases globally. According to the epidemiological studies in Western countries, about 30% of populations are affected by periodontitis [1]. The pathogenesis of periodontitis can be briefly described and summarized as follows: the dental plaque, a bacterial biofilm, induces an inflammatory and immune responses in the adjacent gingival and periodontal or peri-implant tissues. The cells of the immune and inflammatory system are together with resident gingival cells (including fibroblasts, cementoblasts, and epithelial cells, bone cells) triggered to express and release pro-inflammatory cytokines, reactive oxygen species, and matrix metalloproteinases (MMPs) [2–5]. MMPs are genetically distinct but structurally related proteinases that can degrade not only almost all extracellular matrix proteins but also non-matrix bioactive molecules such as growth factors, serpins, insulin receptor, apolipoprotein-1, complement components, and pro- and anti-inflammatory cytokines and chemokines [2–5]. Thus, MMPs can modify immune responses [2–5]. The active form of catalytically competent matrix metalloproteinase-8 (aMMP-8; neutrophil collagenase or collagenase-2) is the predominant MMP in periodontitis-affected gingiva, gingival crevicular fluid (GCF), peri-implant sulcular fluid (PISF), saliva, and mouthrinse [2–5]. MMP-8 cleaves preferably and efficiently the interstitial collagens, mainly type I fibers of the gingival and periodontal tissues, leading to irreversible soft and hard tissue destruction, i.e., the development of periodontal pockets and attachment loss, and eventually leading to tooth loss [2–5]. Physiological levels of MMP-8 in periodontal tissue also participate to protective and anti-inflammatory resolution of infection-induced tissue destruction [6, 7].