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[Osteoclast differentiation regulated by receptor activator of nuclear factor kappaB probably through a novel signaling pathway].
- Source :
-
Zhongguo shi yan xue ye xue za zhi [Zhongguo Shi Yan Xue Ye Xue Za Zhi] 2009 Jun; Vol. 17 (3), pp. 607-11. - Publication Year :
- 2009
-
Abstract
- This study was aimed to investigate the signaling pathways regulating osteoclast (OC) differentiation by receptor activator of nuclear factor kappa (RANK) under physiological condition so as to provide some theoretical basis for clarifying mechanism of bone destruction in multiple myeloma. A mutant TNFR(1)/RANK(2) (named RANK-Mu) chimera consisting of tumor necrosis factor receptor 1 (TNFR(1)) and RANK intramembrane domain was constructed by using deletion mutation for deleting IVVY amino acids in RANK intramembrane domain in accordance with (535-)IVVY(-538) as specific domain regulating OC differentiation by RANK. The RANK-Mu and TNFR(1)/RANK chimera without mutation (RANK-WT) were packaged by using plat E cell line to produce the retrovirus, which were transfected into bone marrow macrophages (BMMs) of TNFR(1)/TNFR(2) double knockout mice. After stimulation of these transfected BMMs with TNF-alpha, the differentiation of BMMs into OCs were observed, meanwhile the phosphorylation of NF-kappab, JNK, p38 and ERK was detected by Western blot after stimulation of these BMMs with TNF-alpha. The results showed that BMMs transfected with RANK-WT could be differentiated into OCs and phosphorylation of NF-kappaB, JNK, P38 and ERK were activated at 5 - 10 minutes after being stimulated by TNFalpha. BMMs transfected with RANK-Mu could not be differentiated into OCs, but phosphorylation of NF-kappaB, JNK, P38 and ERK were activated also. It is concluded that RANK regulates osteoclast differentiation probably not through 4 typical signaling pathways, named as NF-kappaB, JNK, P38 and ERK, in this process other new signaling pathways maybe participate.
- Subjects :
- Animals
Cell Differentiation drug effects
Cell Line, Tumor
Extracellular Signal-Regulated MAP Kinases metabolism
JNK Mitogen-Activated Protein Kinases metabolism
Mice
Mice, Knockout
NF-kappa B metabolism
Osteoclasts cytology
Phosphorylation
Tumor Necrosis Factor-alpha pharmacology
p38 Mitogen-Activated Protein Kinases metabolism
Osteoclasts drug effects
Osteoclasts metabolism
Receptor Activator of Nuclear Factor-kappa B pharmacology
Signal Transduction drug effects
Subjects
Details
- Language :
- Chinese
- ISSN :
- 1009-2137
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Zhongguo shi yan xue ye xue za zhi
- Publication Type :
- Academic Journal
- Accession number :
- 19549373