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. 2021 Mar 3;100(8):798–809. doi: 10.1177/0022034521995157

Figure 2.

Figure 2.

Cellular targets of host modulation agents in periodontitis. Conventional synthetic and biological disease-modifying antirheumatic drugs (DMARDs) are currently being prescribed for the treatment of rheumatoid arthritis. Biological DMARDs inhibit the expression of key proinflammatory markers in periodontitis, such as IL-17 and IL-6, and suppress the proliferation of CD4+ T cells. Rituximab is a monoclonal antibody targeting CD20 that results in the depletion of B cells. Bisphosphonates disrupt osteoclastic activity, inhibit bone degradation, and promote osteoblastic activity. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) regulate fatty acid metabolites of inflammatory cells, suppress proinflammatory gene expression by inhibiting proinflammatory pathways, and decrease the production of inflammatory mediators. n-3 PUFAs are the substrates for the generation of specialized proresolving lipid mediators (SPMs), including resolvins, maresins, and protectins, which orchestrate the active resolution of inflammation. Statins exert their anti-inflammatory and bone-preserving actions by modulating the ERK, MAPK, PI3-Akt, and NF-κB pathways. They also induce the upregulation of SPMs, namely 15-epi-LXA4 and 13-series resolvins, via the LOX-5 and COX-2 enzymatic pathways, respectively, especially when combined with aspirin. Complement inhibitors such as Cp40 suppress osteoclastogenesis and bone loss and decrease IL-17 and the RANKL/OPG ratio in nonhuman primates. Probiotics reduce the production of proinflammatory cytokines by inhibiting the NF-kB pathway and promote the accumulation of Tregs by inhibiting histone deacetylases. SPMs downregulate cytokines/chemokines and promote bone regeneration. D-resolvins antagonize IL-17, induce the expression of the endothelial anti-inflammatory marker Del-1 through the GSK-3b-C/EBPb pathway, and decrease CD4+ cells. SPMs restore viability, proliferation, and migration of human PDLSCs and enhance differentiation of cementoblasts/osteoblasts. IL, interleukin; PDLSC, periodontal ligament stem cell.