Cot/Tpl2对于成骨细胞中脂多糖诱导的RANKL生成至关重要。

Cot/Tpl2 is essential for RANKL induction by lipid A in osteoblasts.

作者信息

Kikuchi T, Yoshikai Y, Miyoshi J, Katsuki M, Musikacharoen T, Mitani A, Tanaka S, Noguchi T, Matsuguchi T

机构信息

Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

出版信息

J Dent Res. 2003 Jul;82(7):546-50. doi: 10.1177/154405910308200712.

DOI:10.1177/154405910308200712

PMID:12821717

Abstract

Lipopolysaccharide (LPS) is a pathogenic factor that increases bone resorption in periodontal diseases. LPS treatment of osteoblasts was shown to induce the receptor activator of NF-kappa B ligand (RANKL), an essential secretory or membrane-bound factor for osteoclast function, in a manner dependent on extracellular signal-regulated kinase (ERK) activation. However, the mechanisms regulating this process remained unknown. Here, we show that RANKL mRNA induction and ERK activation, when treated with synthetic lipid A (an active center of LPS), were markedly reduced in mouse osteoblasts lacking Cot/Tpl2, which was recently recognized as an essential kinase for the induction of TNF-alpha by LPS in macrophages. In contrast, c-Jun N-terminal kinase (JNK), p38 kinase, Raf-1, and NF-kappa B were normally activated in cot/tpl2-/- osteoblasts. These findings indicate that Cot/Tpl2 is essential for LPS-induced ERK activation and RANKL induction in osteoblasts.

摘要

脂多糖（LPS）是一种致病因素，可增加牙周疾病中的骨吸收。研究表明，LPS处理成骨细胞可诱导核因子κB受体激活蛋白配体（RANKL），这是破骨细胞功能所必需的分泌型或膜结合型因子，其诱导方式依赖于细胞外信号调节激酶（ERK）的激活。然而，调节这一过程的机制仍不清楚。在此，我们发现，在用合成脂质A（LPS的活性中心）处理时，缺乏Cot/Tpl2的小鼠成骨细胞中RANKL mRNA的诱导和ERK的激活显著降低，Cot/Tpl2最近被认为是LPS在巨噬细胞中诱导肿瘤坏死因子-α所必需的激酶。相反，在cot/tpl2-/-成骨细胞中，c-Jun氨基末端激酶（JNK）、p38激酶、Raf-1和核因子κB通常被激活。这些发现表明，Cot/Tpl2对于LPS诱导成骨细胞中的ERK激活和RANKL诱导至关重要。