Table of Contents
Journal of Signal Transduction
Volume 2012, Article ID 308943, 17 pages
http://dx.doi.org/10.1155/2012/308943
Review Article

MAPK Usage in Periodontal Disease Progression

1Department of Endodontics, Periodontics and Oral Medicine, The First People’s Hospital of Yunnan Province, Kunming, Yunnan 650032, China
2Department of Craniofacial Biology and Center for Oral Health Research, Medical University of South Carolina, Charleston, SC 29425, USA

Received 15 August 2011; Accepted 5 October 2011

Academic Editor: Fred Schaper

Copyright © 2012 Qiyan Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 p38α inhibitor 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.