Revisiting the Page & Schroeder model: the good, the bad and the unknowns in the periodontal host response 40 years later

Abstract

In their classic 1976 paper, Page & Schroeder described the histopathologic events and the types of myeloid cells and lymphocytes involved in the initiation and progression of inflammatory periodontal disease. The staging of periodontal disease pathogenesis as ‘initial’, ‘early’, ‘established’ and ‘advanced’ lesions, productively guided subsequent research in the field and remains fundamentally valid. However, major advances regarding the cellular and molecular mechanisms underlying the induction, regulation, and effector functions of immune and inflammatory responses necessitate a reassessment of their work and its integration with emerging new concepts. We now know that each type of leukocyte is actually represented by functionally distinct subsets with different or even conflicting roles in immunity and inflammation. Unexpectedly, neutrophils, traditionally regarded as merely anti-microbial effectors in acute conditions and protagonists of the ‘initial’ lesion, are currently appreciated for their functional versatility and critical roles in chronic inflammation. Moreover, an entirely new field of study, osteoimmunology, has developed and shed light on the impact of immunoinflammatory events on the skeletal system. These developments and the molecular dissection of crosstalk interactions between innate and adaptive leukocytes, as well as between the immune system and local homeostatic mechanisms, offer a more nuanced understanding of the host response in periodontitis with profound implications for treatment. At the same time, deeper insights have generated new questions many of which remain unanswered. In this review, forty years after Page & Schroeder proposed their model, we summarize enduring and emerging advances in periodontal disease pathogenesis.

Analysis of salivary phenotypes of generalized aggressive and chronic periodontitis through nuclear magnetic resonance‐based metabolomics

“…A major challenge in clinical periodontology is to find a reliable molecular marker of tissue destruction with high sensitivity, specificity and utility. At present, there is still a certain level of noise in metabolites fluctuation occurring in the periodontal microenvironment during the pathogenesis of periodontitis, that is not currently understood . The hurdle in identifying neat pathological phenotypes is because of the intrinsic heterogeneity of periodontal diseases and the inherent complexity underlying .…”

Comparison of miRNA expression profiles in individuals with chronic or aggressive periodontitis

“…The severity of the disease depends, in some way, on the balance and interactions between the bacterial challenge and the host immunoinflammatory response, influenced by modifiable and non‐modifiable environmental and host risk factors (Kinane et al, ; Kornman, ). The mechanisms of immunoinflammatory regulation in periodontitis are complex, and host modulation has been recently reviewed (Bartold & Van Dyke, ; Hajishengallis & Korostoff, ). The role of miRNAs in the pathobiology of periodontal diseases has also been recently explored (Kebschull & Papapanou, ), demonstrating specific roles of miRNAs in regulating gene expression and affecting different cellular and molecular pathways in periodontal homeostasis and disease.…”

Herpesvirus‐bacteria synergistic interaction in periodontitis

“…The association of A. actinomycetemcomitans and P. gingivalis with severe periodontitis was established in Buffalo, New York, in the late 1970s, and virulence factors and the immune response of the same bacteria were published soon thereafter in 1984 . Studies on the pathogenicity of A. actinomycetemcomitans and P. gingivalis have continued unabated until the current time . Aggregatibacter actinomycetemcomitans is a toxin‐producing species of bacteria, and P. gingivalis is a strongly proteolytic species.…”