Cot/Tpl2 is Essential for RANKL Induction by Lipid A in Osteoblasts

• Published in: Journal of dental research 2003-07, Vol.82 (7), p.546-550
• Main Authors: Kikuchi, T., Yoshikai, Y., Miyoshi, J., Katsuki, M., Musikacharoen, T., Mitani, A., Tanaka, S., Noguchi, T., Matsuguchi, T.
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Northern; Cell Differentiation; Cells, Cultured; Dentistry; Enzyme Activation - drug effects; Glycoproteins - biosynthesis; Lipid A - pharmacology; MAP Kinase Kinase Kinases - metabolism; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases - metabolism; Osteoblasts - drug effects; Osteoblasts - enzymology; Osteoclasts - cytology; Osteoprotegerin; Proto-Oncogene Proteins - metabolism; Receptors, Cytoplasmic and Nuclear - biosynthesis; Receptors, Tumor Necrosis Factor - biosynthesis; RNA, Messenger - analysis; Up-Regulation - drug effects
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/154405910308200712

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.