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Targeting MAPK/MKP Signaling as a Therapeutic Axis in Periodontal Disease

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Emerging Therapies in Periodontics

Abstract

Periodontal pathogens stimulate inflammatory cytokine and chemokine production within the periodontal microenvironment producing chronic inflammation and subsequent bone loss. In stimulated cells, the maximal induction of cytokine/chemokine expression requires activation of the p38 mitogen-activated protein kinase (MAPK) pathways. The clinical relevance of p38 MAPK activation was demonstrated by our group where excessive MAPK correlated with human periodontal disease severity. Importantly, MAPK signaling contributes toward the expression of multiple gene targets including (interleukin)-1β, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-13, receptor activator of nuclear factor kappa-Β (RANKL), and other inflammatory mediators that can contribute toward periodontal inflammation and bone destruction. Once MAPK activation and substrate phosphorylation occur, MAPK inactivation occurs through specific phosphatase activity via a family of dual-specificity MAPK phosphatases (MKPs) that target the regulatory sites of these kinases. In this chapter, the therapeutic potential to control the MAPK/MKP signaling axis of innate immunity is explored through various therapeutic platforms including small molecule inhibitors, RNA interference, gene therapy, and nanoparticle encapsulation of small molecules.

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Acknowledgments

This work was supported by the National Institutes of Health (NIH) grants 1 R01DE028258 and 1 R21DE027017.

Disclosure of Interest: There are no conflicts of interest to disclose.

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  1. Department of Oral Biology, University at Buffalo, Buffalo, NY, USA

    Keith L. Kirkwood

  2. Department of Head & Neck/Plastic & Reconstructive Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Keith L. Kirkwood

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  1. School of Dental Medicine, Department of Periodontics, University of Pennsylvania, Philadelphia, PA, USA

    Sinem Esra Sahingur

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Kirkwood, K.L. (2020). Targeting MAPK/MKP Signaling as a Therapeutic Axis in Periodontal Disease. In: Sahingur, S. (eds) Emerging Therapies in Periodontics. Springer, Cham. https://doi.org/10.1007/978-3-030-42990-4_5

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