MAPK Usage in Periodontal Disease Progression
Open Access
- 23 January 2012
- journal article
- Published by Hindawi Limited in Journal of Signal Transduction
- Vol. 2012, 1-17
- https://doi.org/10.1155/2012/308943
Abstract
In periodontal disease, host recognition of bacterial constituents, including lipopolysaccharide (LPS), induces p38 MAPK activation and subsequent inflammatory cytokine expression, favoring osteoclastogenesis and increased net bone resorption in the local periodontal environment. In this paper, we discuss evidence that the p38/MAPK-activated protein kinase-2 (MK2) signaling axis is needed for periodontal disease progression: an orally administered p38αinhibitor reduced the progression of experimental periodontal bone loss by reducing inflammation and cytokine expression. Subsequently, the significance of p38 signaling was confirmed with RNA interference to attenuate MK2-reduced cytokine expression and LPS-induced alveolar bone loss. MAPK phosphatase-1 (MKP-1), a negative regulator of MAPK activation, was also critical for periodontal disease progression. In MPK-1-deficient mice, p38-sustained activation increased osteoclast formation and bone loss, whereas MKP-1 overexpression dampened p38 signaling and subsequent cytokine expression. Finally, overexpression of the p38/MK2 target RNA-binding tristetraprolin (TTP) decreased mRNA stability of key inflammatory cytokines at the posttranscriptional level, thereby protecting against periodontal inflammation. Collectively, these studies highlight the importance of p38 MAPK signaling in immune cytokine production and periodontal disease progression.Keywords
Funding Information
- National Institutes of Health (1R01DE021423, 1R01DE018290, 2P20 RR017696, T32 DE017551)
This publication has 156 references indexed in Scilit:
- Tristetraprolin Regulates Interleukin-6 Expression Through p38 MAPK-Dependent Affinity Changes with mRNA 3′ Untranslated RegionJournal of Interferon & Cytokine Research, 2011
- Silencing Mitogen-Activated Protein Kinase-Activated Protein Kinase-2 Arrests Inflammatory Bone LossThe Journal of pharmacology and experimental therapeutics, 2010
- Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone lossGene Therapy, 2010
- Targeting mRNA Stability Arrests Inflammatory Bone LossMolecular Therapy, 2008
- p38α Stabilizes Interleukin-6 mRNA via Multiple AU-richElementsOnline Journal of Public Health Informatics, 2008
- A dominant function of p38 mitogen‐activated protein kinase signaling in receptor activator of nuclear factor‐κB ligand expression and osteoclastogenesis induction by Aggregatibacter actinomycetemcomitans and Escherichia coli lipopolysaccharideJournal of Periodontal Research, 2007
- Novel host response therapeutic approaches to treat periodontal diseasesPeriodontology 2000, 2007
- Pathogen Recognition and Innate ImmunityCell, 2006
- p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseasesNature Reviews Drug Discovery, 2003
- Natural history of periodontal disease in manJournal of Clinical Periodontology, 1986