Periodontal disease: linking the primary inflammation to bone loss

Abstract

Periodontal disease (PD), or periodontitis, is defined as a bacterially induced disease of the tooth-supporting (periodontal) tissues. It is characterized by inflammation and bone loss; therefore understanding how they are linked would help to address the most efficacious therapeutic approach. Bacterial infection is the primary etiology but is not sufficient to induce the disease initiation or progression. Indeed, bacteria-derived factors stimulate a local inflammatory reaction and activation of the innate immune system. The innate response involves the recognition of microbial components by host cells, and this event is mediated by toll-like receptors (TLRs) expressed by resident cells and leukocytes. Activation of these cells leads to the release of proinflammatory cytokines and recruitment of phagocytes and lymphocytes. Activation of T and B cells initiates the adaptive immunity with Th1 Th2 Th17 Treg response and antibodies production respectively. In this inflammatory scenario, cytokines involved in bone regulation and maintenance have considerable relevance because tissue destruction is believed to be the consequence of host inflammatory response to the bacterial challenge. In the present review, we summarize host factors including cell populations, cytokines, and mechanisms involved in the destruction of the supporting tissues of the tooth and discuss treatment perspectives based on this knowledge.

Figures

Figure 1

The network of cytokines, released by resident and migrating cells (lymphocytes and phagocytes), involved in periodontal bone resorption. Resident cells including epithelial cells (ECs), gingival fibroblast (GFs), periodontal ligament fibroblasts (PDLFs), osteoblast, and dendritic cells mediate the Innate Immunity. They respond to the bacterial challenge (via TLRs) by producing proinflammatory cytokines and chemokines. ECs produce IL-8, a neutrophil chemoattractant, which recruits neutrophils (neu) and increases monocyte (mono) adhesion. Neu in turn produces IL-1, IL-6, and TNF-α, while Mono can differentiate into osteoclasts (OCs). DCs produce IL-12 and IL-18 but also act as antigen-presenting cells for B and T Cells. GFs produce IL-8, TNF-α, and IL-6. PDLFs produce IL-1β, IL-6, TNF-α, and RANKL. Microorganisms can go deeper in the periodontal tissue and reach the surface of alveolar bone, promoting the expression of the proosteoclastogenic cytokine RANKL by osteoblasts (OBs). These inflammatory cytokines are directly (as RANK-L and TNF-α) or indirectly involved in osteoclastogenesis and are responsible for the alveolar bone loss. After this initial response (lasting approximately 21 days), activation of T and B cells by antigen-presenting cells initiates the adaptive immunity. As a result, tissues affected by periodontitis become colonized with both lymphocyte subtypes, but with a larger proportion of B cells than T cells. The majority of B cells in periodontal lesions are RANKL+. T cells produce the proosteoclastogenic cytokines RANKL and TNF-α, and IL-17 which exerts its osteoclastogenic activity by enhancing RANKL expression on osteoblasts. Furthermore a new role for TRAIL, produced in periodontitis, is emerging in promoting osteoclastogenesis and favoring OBs apoptosis.