Molecular Biotypes for Periodontal Diseases?

Since the introduction of 2 forms of periodontitis, chronic periodontitis (CP) and aggressive periodontitis (AgP) (Armitage, 1999), based on major differences in clinical phenotypes, questions still remain regarding the exact biological features that correspond to the separation of destructive periodontal disease into these 2 entities. Why not just one form, or why not at least 4 types based on age of onset (Van der Velden, 2000)? Scherp (1964), in his notable epidemiological survey on periodontitis, wrote that “the varieties of periodontal disease are almost limitless, depending on one’s taste for subclassification.” Periodontitis diagnosis and classification continue to be under debate (Van der Velden, 2005; Armitage and Cullinan, 2010). An interesting study in the current issue of the Journal of Dental Research (Kebschull et al., 2013) proposed that there are characteristic gene expression signatures (transcriptomes) in gingival biopsies from CP and AgP. These molecular patterns are distinctive between the 2 disease forms and possibly could identify characteristic features and specific pathophysiology pathways. To date, no unequivocal histopathological or clear microbiological features have been found to establish a clear biological basis for the distinction between CP and AgP (Armitage, 2010; Smith et al., 2010). Although Kebschull et al. (2013) observed differences in gene expression profiles between CP and AgP, the authors also rightfully wrote that the CP and AgP lesions displayed surprisingly limited differences: for AgP, “the magnitude of the differences was generally modest, with 30 over-expressed and only one under-expressed probe by an absolute change of >1.5 fold in AgP vs. CP lesions.” How to put this into perspective? Obviously, gene expression signatures per se may not really reflect the complex pathophysiological pathways of periodontitis; they may merely reflect in both CP and AgP, closely resembling “end points” of immune and tissue physiologies in response to a given biofilm. For example, the experimental gingivitis study by Offenbacher et al. (2009) showed, also with transcriptomic signatures from gingival biopsies, the up-regulation of genes in response to the increasing dental plaque mass. Periodontitis is a complex disease, where multiple causal factors play simultaneous and interactive roles (Laine et al., 2012). There are 4 main causal risk factors, i.e., the intriguing dental and subgingival microbiota (the bacterial biofilm), individual genetic variations, lifestyle, and systemic factors. Complexity is not just a word to describe our inability to cope with a large number of parameters involved in a system. Complexity has now been found to be a fundamental law in nature, rooted to almost every phenomenon we observe, even those appearing to be simple (Nicolis and Nicolis, 2012). There are several attributes of complexity that are well-recognized: