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Updated: May 25, 2026
Inducing Apical Periodontitis in Mice
Published on: August 6, 2019
MAPK usage in periodontal disease progression
Qiyan Li1, Michael S Valerio, Keith L Kirkwood
1Department of Endodontics, Periodontics and Oral Medicine, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, China.
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.
Insights
Targeting the p38 MAPK signaling pathway, crucial in periodontal disease, can reduce bone loss. Inhibiting p38 MAPK activation and related molecules effectively decreases inflammation and cytokine expression, offering a potential therapeutic strategy for periodontitis.
Area of Science:
- Periodontology
- Immunology
- Molecular Biology
Background:
- Periodontal disease involves bacterial recognition, leading to p38 MAPK activation and inflammatory cytokine release.
- This process promotes osteoclastogenesis and bone resorption in the periodontal tissues.
Purpose of the Study:
- To investigate the role of the p38/MAPK-activated protein kinase-2 (MK2) signaling axis in periodontal disease progression.
- To evaluate the therapeutic potential of targeting this pathway for treating periodontal inflammation and bone loss.
Main Methods:
- Utilized an orally administered p38α inhibitor in experimental models of periodontal disease.
- Employed RNA interference to attenuate MK2 and studied the effects of MAPK phosphatase-1 (MKP-1) deficiency and overexpression.
- Investigated the impact of tristetraprolin (TTP) on inflammatory cytokine mRNA stability.
Main Results:
- Oral p38α inhibition significantly reduced periodontal bone loss by decreasing inflammation and cytokine levels.
- MK2 attenuation and MKP-1 deficiency exacerbated LPS-induced alveolar bone loss, while MKP-1 overexpression offered protection.
- Overexpression of TTP stabilized inflammatory cytokine mRNA, mitigating periodontal inflammation.
Conclusions:
- The p38 MAPK signaling pathway, including MK2 and MKP-1, is critical for periodontal disease progression.
- Targeting p38 MAPK signaling and its downstream effectors like TTP presents a promising therapeutic avenue for periodontal disease.
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