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

First Author  Kikuchi T Year  2003
Journal  J Dent Res Volume  82
Issue  7 Pages  546-50
PubMed ID  12821717 Mgi Jnum  J:187216
Mgi Id  MGI:5435880 Doi  10.1177/154405910308200712
Citation  Kikuchi T, et al. (2003) Cot/Tpl2 is essential for RANKL induction by lipid A in osteoblasts. J Dent Res 82(7):546-50
abstractText  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.
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