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Review
. 2007:43:294-315.
doi: 10.1111/j.1600-0757.2006.00166.x.

Novel host response therapeutic approaches to treat periodontal diseases

Keith L Kirkwood  1 , Joni A Cirelli, Jill E Rogers, William V Giannobile
Affiliations
Review

Novel host response therapeutic approaches to treat periodontal diseases

Keith L Kirkwood et al. Periodontol 2000. 2007.
No abstract available

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Figures

Fig. 1
Fig. 1
Toll-like receptor (TLR) signaling: stimulation of TLRs by periodontal pathogen associated molecular patterns triggers the association of myleloid differentiation primary-response protein 88 (MyD88), which in turn recruits IL-1 receptor associated kinase-4 (IRAK) [which phosphorylates IRAK1 (represented by IRAK)]. Tumor-necrosis factor receptor associated factor-6 (TRAF6) is also recruited to the phosphorylated IRAK complex. IRAK/TRAF6 then dissociate from the receptor complex to a new complex with transforming growth factor β-activated kinase (TAK1) along with TAK-1 and -2 binding protein (TAB1 and -2) (data not shown) which phosphorylate TAK1. TAK1, in turn, phosphorylates both mitogen activated protein kinase kinases-3 and -6 (MKK3, MKK6) and the inhibitor of nuclear factor κB (IκB)-kinase complex (IKK complex) (data not shown). The IKK complex then phosphorylates IκB, which allows nuclear factor-kappa B (NF-κB) transcription factors (p50/p65) to translocate to the nucleus and induce gene expression of cytokine genes. Similarly, MKK3/6 can phosphorylate p38 mitogen-activated protein kinase (MAPK) to activate activator protein-1 transcription factors and initiate gene expression. In addition, p38 can phosphorylate RNA-binding proteins, which can stabilize cytokine mRNA and thus amplify cytokine production. AP1, activating protein-1; ERK, extracellular signal-regulated kinases; MEK, MAPK/ERK kinase; SRE, serum response element.
Fig. 2
Fig. 2
Potential therapeutic strategies to treat bone resorption: agents that block the differentiation or activity of osteoclasts are potential therapeutic agents. Osteoprotegerin (OPG) inhibits the differentiation of osteoclasts through its action as a decoy receptor that blocks receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) and RANK juxtacrine interaction. Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory molecules [including p38 mitogen-activated protein kinase (MAPK) inhibitors, c-jun N-terminal kinase (JNK) inhibitors and NF-κB inhibitors] can inhibit the formation of hematoprogenitor cells to pre-osteoclasts. Antibodies to RANKL can also block this interaction. Matrix metalloproteinase (MMP) inhibitors reduce the protease degradation of the organic matrix, and anti-integrins block the initial osteoclast adhesion to the matrix. IL, interleukin; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; sRANKL, soluble RANKL; TNF-α, tumor necrosis factor-α; TNFsRC, TNF soluble receptor.
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