Periodontal disease is caused primarily by oral bacterial infections (Loos and Van Dyke, 2020). Dental plaque, a biofilm comprised of a complex microbial community which grows on tooth surfaces, may trigger an inflammatory response in periodontal tissue (Filoche
Resistance to antibiotics is the major side effect in treating periodontal disease. Excessive use of antibiotics can selectively increase several antibiotic-resistant periodontal microorganisms (Sheridan
Injury of the human body results in a sequential cascade of events that includes immune and inflammatory responses. Inflammasome, a cytosolic multiprotein oligomer of the innate immune system, mediates the body’s inflammatory response to injury. Normal inflammasome assembly induces proteolytic cleavage, maturation, and production of pro-inflammatory cyto­kine such as interleukin, while abnormal inflammasome activation may result in the development of various diseases, including cancer, autoimmune, and metabolic disease. During normal inflammasome production, the priming procedure is ini­tiated by stimulation of nuclear factor (NF)-kB via lipopolysaccharide (LPS) or tumor necrosis factor-b induced expression of inflammasome’s components. After priming is completed and once an activation signal is received, inflammasome multimerizes and autoactivates caspase-1. Different signals are used to activate the production of over 10 distinct types of in­flammasome. Among these, NODs and NACHT-leucine-rich repeats (NLRs), absent in melanoma 2-like receptor (ALR), and Pyrin inflammasome are associated with periodontal disease pathogenesis (Marchesan
NLR inflammasome (NLRP1 and NLRP3): NODs and NACHT leucine rich repeats (NLRs) are a large family of intracellular proteins regulating innate immune responses. In one clinical study, NLRP1 was found to be present at low levels in healthy gingiva and at elevated levels in the epithelium and connective tissue of aggressive periodontitis (Xue
ALR inflammasome (IFI16 and AIM2): Absent in melanoma 2-like receptors (ALRs) are a family of DNA-binding proteins containing DNA-binding domains and pyrin. In one clinical study, levels of absent in melanoma 2 (AIM2) were elevated in patients experiencing chronic periodontitis (Xue
Teriparatide (FORTEO®): Teriparatide (FORTEO®) which con­sists of the bioactive portion of parathyroid hormone (PTH), was the first anabolic drug approved by the FDA to treat osteoporosis. Because PTH plays a role in the WNT/β-catenin signaling that downregulates sclerostin, which is an inhibitor of WNT-LRP5/6, and stimulates bone formation, Teriparatide is a research target among periodontists as a potential means of achieving alveolar bone regeneration (Jilka
Sclerostin antibody: Second only to bone morphogenetic proteins, the Wnt/β-catenin signaling pathway has received much attention due to its importance in osteoblast differentiation and bone formation (Baron and Kneissel, 2013). Similar to other signaling mechanisms, Wnt signaling is also regulated by an agonist and antagonist. Sclerostin, encoded by the SOST gene, is primarily expressed in the osteocyte and achieves an anti-anabolic effector by inhibiting Wnt signaling. Historically, it was believed that sclerostin was a BMP antagonist (Winkler
Periodontitis is a bacterial-associated and host-mediated multifactorial inflammatory disease. Although the overall phenotype of chronic periodontitis may be similar across patients, the underlying causes of the disease varies from person to person. Traditional periodontal treatment fails primarily when local inflammation caused by bacterial invasion is met with an uncontrolled host immune response. Novel responses to periodontitis will require an understanding of individual molecular pathogenesis and the development of target-oriented therapeutic drugs.
The recent focus on inhibiting plaque biofilm formation with QSIs may result in the development of new drugs for periodontal treatment. Moreover, as inflammasomes and their components (NLR, ALR, and Pyrin) are associated with the onset of periodontal disease, drugs that directly target the inflammasome and relieve periodontal inflammation may be developed. Finally, two anabolic agents that inhibit bone loss and promote bone regeneration may be useful in treating advanced cases of periodontitis. Preclinical studies have shown that Teriparatide and sclerostin antibody are both effective in periodontitis.
Of course, the safety and effectiveness of any of these drugs must be verified before being widely adopted. As this review has shown, however, there is a sound argument to be made that these potential treatments are ready for the next stage of testing; multicenter human clinical trial studies.
This work was supported by Fund of Biomedical Research Institute, Jeonbuk National University Hospital (SH) and by the Technology Innovation Program (20012892) funded by the Ministry of Trade, Industry & Energy (MOTIE) of Korea (YS).