MAPK usage in periodontal disease progression.
MAPK usage in periodontal disease progression.
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DOI：
10.1155/2012/308943
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Kirkwood KL
中科院分区：
文献类型：
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作者：
Li Q;Valerio MS;Kirkwood KL
在牙周病中，宿主识别细菌成分，包括脂多糖（LPS），诱导p38 MAPK激活和随后的炎性细胞因子表达，有利于破骨细胞生成和增加净骨吸收在局部牙周环境。在这篇文章中，我们讨论了p38/MAPK活化蛋白激酶-2（MK2）信号轴是牙周病进展所必需的证据：口服p38α抑制剂通过减少炎症和细胞因子表达来减少实验性牙周骨丢失的进展。随后，证实了p38信号的意义与RNA干扰减弱MK 2减少细胞因子的表达和LPS诱导的牙槽骨丢失。MAPK磷酸酶-1（MKP-1）是MAPK激活的负调节因子，对牙周病的进展也至关重要。在MPK-1缺陷小鼠中，p38持续激活增加破骨细胞形成和骨丢失，而MKP-1过表达抑制p38信号传导和随后的细胞因子表达。最后，p38/MK2靶RNA结合tristetraprolin（TTP）的过表达在转录后水平降低了关键炎性细胞因子的mRNA稳定性，从而保护牙周炎症。总的来说，这些研究强调了p38 MAPK信号在免疫细胞因子产生和牙周病进展中的重要性。
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.