Maintaining homeostatic control of periodontal bone tissue

Abstract

Alveolar bone is a unique osseous tissue due to the proximity of dental plaque biofilms. Periodontal health and homeostasis are mediated by a balanced host immune response to these polymicrobial biofilms. Dysbiotic shifts within dental plaque biofilms can drive a proinflammatory immune response state in the periodontal epithelial and gingival connective tissues, which leads to paracrine signaling to subjacent bone cells. Sustained chronic periodontal inflammation disrupts "coupled" osteoclast-osteoblast actions, which ultimately result in alveolar bone destruction. This chapter will provide an overview of alveolar bone physiology and will highlight why the oral microbiota is a critical regulator of alveolar bone remodeling. The ecology of dental plaque biofilms will be discussed in the context that periodontitis is a polymicrobial disruption of host homeostasis. The pathogenesis of periodontal bone loss will be explained from both a historical and current perspective, providing the opportunity to revisit the role of fibrosis in alveolar bone destruction. Periodontal immune cell interactions with bone cells will be reviewed based on our current understanding of osteoimmunological mechanisms influencing alveolar bone remodeling. Lastly, probiotic and prebiotic interventions in the oral microbiota will be evaluated as potential noninvasive therapies to support alveolar bone homeostasis and prevent periodontal bone loss.

Keywords: alveolar bone; microbiota; osteoimmunology; periodontal disease.

FIGURE 1

Murine alveolar bone anatomy. Twelve-week-old male C57BL6 mouse: serial frontal sections. A, Through the mesial root of the mandibular first molar. B, Through the furcation of the mandibular first molar. P, periosteum; E, endosteum; B.Ct.B, buccal cortical bone; L.Ct.B, lingual cortical bone; Ma, marrow; Tb.B, trabecular bone

FIGURE 2

Bone cells: osteoclasts, osteoblasts, and osteocytes. Twelve-week-old male C57BL6 mouse trabecular bone. Tartrate-resistant acid phosphatase–positive osteoclasts (red arrows) resorbing old bone, cuboidal bone forming osteoblasts (green arrows), and bone-embedded osteocytes (black arrows)

FIGURE 3

Periodontal immune microenvironment. Subgingival plaque biofilm derived microbe-associated molecular patterns stimulate the periodontal immune response. Neutrophils are recruited to the junctional epithelium via chemokine gradients. Innate immune cells, such as macrophages and dendritic cells, secrete matrix metalloproteinases and proinflammatory cytokines—that is, tumor necrosis factor (TNF), interleukin-1 (IL-1), interleukin-6 (IL-6)—which disrupt connective tissue homeostasis. Osteoblasts, osteocytes, periodontal ligament cells, and lymphocytes (ie, T cells, B cells) secrete receptor activator of nuclear factor-kappa B ligand (RANKL) and other proinflammatory factors, which support osteoclastogenesis and inhibit osteoblastogenesis. B cells synthesize antibodies that drive the humoral response. Osteocytes secrete sclerostin to suppress osteoblastogenesis. CEJ, cementoenamel junction; DC, dendritic cells; IFNy, interferon-gamma; Mac, macrophages; MAMPs, microbe-associated molecular patterns; MMP, matrix metalloproteinases; OB, osteoblasts; OC, osteoclasts; OPG, osteoprotegrin; PDL, periodontal ligament; PMN, neutrophils; SOST, sclerostin

FIGURE 4

Localized periodontitis at maxillary right first molar. Apical migration of subgingival biofilm–mediated alveolar bone destruction at the distobuccal root

FIGURE 5

Periodontal osteoimmunology. The subgingival plaque biofilm induces a multitude of immune cells to mount the periodontal immune response. There is an increase in neutrophil chemotaxis, as well as differentiation of naive CD4⁺ T cells into several subsets. T_H1 cells secrete interferon-gamma (IFNγ), which can have pro-osteoclastogenic properties. T_H17 cells secrete interleukin-17 (IL-17) and tumor necrosis factor (TNF), which induce osteoblasts to synthesize proinflammatory/pro-osteoclastic factors. T regulatory cells and T_H2 cells secrete interleukin-10 (IL-10) and interleukin-4 (IL-4), which have anti-osteoclastogenic effects. T_H22 cells and T_H9 cells produce interleukin-22 (IL-22) and interleukin-9 (IL-9), factors that currently have unclear roles in periodontal osteoimmunology. B cells, natural killer (NK) cells, and natural killer T (NKT) cells can secrete receptor activator of nuclear factor-kappa B ligand (RANKL), whereas mast cells can produce interleukin-17 (IL-17) to support osteoclastogenesis. Myeloid-lineage cells, such as myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells (DC), synthesize proinflammatory cytokines—that is, TNF, interleukin-1 (IL-1), interleukin-6 (IL-6)—that support osteoclastogenesis. M-CSF, macrophage colony-stimulating factor; T_REG, T regulatory cells