Inflammation and regeneration in the dentin-pulp complex: a double-edged sword.
Dental tissue infection and disease result in acute and chronic activation of the innate immune response, which is mediated by molecular and cellular signaling. Different cell types within the dentin-pulp complex are able to detect invading bacteria at all stages of the infection. Indeed, at relatively early disease stages, odontoblasts will respond to bacterial components, and as the disease progresses, core pulpal cells including fibroblasts, stems cells, endothelial cells, and immune cells will become involved. Pattern recognition receptors, such as Toll-like receptors expressed on these cell types, are responsible for detecting bacterial components, and their ligand binding leads to the activation of the nuclear factor-kappa B and p38 mitogen-activated protein (MAP) kinase intracellular signaling cascades. Subsequent nuclear translocation of the transcription factor subunits from these pathways will lead to proinflammatory mediator expression, including increases in cytokines and chemokines, which trigger host cellular defense mechanisms. The complex molecular signaling will result in the recruitment of immune system cells targeted at combating the invading microbes; however, the trafficking and antibacterial activity of these cells can lead to collateral tissue damage. Recent evidence suggests that if inflammation is resolved relatively low levels of proinflammatory mediators may promote tissue repair, whereas if chronic inflammation ensues repair mechanisms become inhibited. Thus, the effects of mediators are temporal context dependent. Although containment and removal of the infection are keys to enable dental tissue repair, it is feasible that the development of anti-inflammatory and immunomodulatory approaches, based on molecular, epigenetic, and photobiomodulatory technologies, may also be beneficial for future endodontic treatments.
Oral Biology, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address: p.r.cooper@bham.ac.uk.
Paul R
PR
Cooper
Oral Biology, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Michelle J
MJ
Holder
Oral Biology, School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Anthony J
AJ
Smith
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001419:Bacteria / Q000276:immunology; D003782:Dental Pulp / Q000276:immunology*; D003804:Dentin / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D011671:Pulpitis / Q000276:immunology*; D012038:Regeneration / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators
Dentin; enamel; epigenetic; extracellular matrix; histone deacetylase inhibitors; interleukins; low-level light therapy; migration; pulp; reactive oxygen species