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

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

    Research output: Contribution to journalArticlepeer-review

    20 Citations (Scopus)


    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-κB 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-α by LPS in macrophages. In contrast, c-Jun N-terminal kinase (JNK), p38 kinase, Raf-1, and NF-κB 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.

    Original languageEnglish
    Pages (from-to)546-550
    Number of pages5
    JournalJournal of Dental Research
    Issue number7
    Publication statusPublished - Jul 2003

    All Science Journal Classification (ASJC) codes

    • General Dentistry


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