| RRC ID |
73044
|
| 著者 |
Ishida A, Fujita N, Kitazawa R, Tsuruo T.
|
| タイトル |
Transforming growth factor-beta induces expression of receptor activator of NF-kappa B ligand in vascular endothelial cells derived from bone.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Vascular endothelial cells in bone are thought to have significant roles on pathological bone resorption such as bone metastasis and hypercalcemia because this resorption is often seen where blood vessels are abundant. However, the detailed mechanisms have not yet been elucidated. Here, we focused on transforming growth factor-beta (TGF-beta) and studied its effects on vascular endothelial cells because TGF-beta is abundantly stored in bone matrix and is released and activated during bone resorption. We found that TGF-beta up-regulated the expression of receptor activator of NF-kappa B ligand (RANKL) mRNA and protein in bone marrow-derived endothelial cells and in primary vascular endothelial cells but not in osteoblasts. Further analysis revealed that TGF-beta promoted phosphorylation of cAMP response element-binding protein and p38. Protein kinase A inhibitor KT5720 and p38 inhibitor SB203580 significantly reduced the TGF-beta-induced RANKL expression. Moreover, we found two CRE-like domains in murine RANKL promoter region that were critical for TGF-beta-dependent RANKL expression. Therefore, protein kinase A and p38 signaling pathways are involved in TGF-beta-induced RANKL expression by stimulating transcription factors that bind to the CRE-like domains. Our findings indicate that TGF-beta stimulates osteoclastogenesis by promoting RANKL expression in endothelial cells under pathological conditions.
|
| 巻・号 |
277(29)
|
| ページ |
26217-24
|
| 公開日 |
2002-7-19
|
| DOI |
10.1074/jbc.M111093200
|
| PII |
S0021-9258(19)66362-3
|
| PMID |
12011070
|
| MeSH |
Animals
Bone and Bones / cytology
Bone and Bones / metabolism*
Carbazoles*
Carrier Proteins / biosynthesis*
Carrier Proteins / genetics
Cells, Cultured
Cyclic AMP Response Element-Binding Protein / metabolism
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Dinoprostone / metabolism
Endothelium, Vascular / metabolism*
Enzyme Inhibitors / pharmacology
Humans
Imidazoles / pharmacology
Indoles / pharmacology
Membrane Glycoproteins / biosynthesis*
Membrane Glycoproteins / genetics
Mice
Mitogen-Activated Protein Kinases / metabolism
NF-kappa B / metabolism*
Osteoclasts / metabolism
Phosphorylation
Promoter Regions, Genetic
Pyridines / pharmacology
Pyrroles / pharmacology
RANK Ligand
RNA, Messenger / metabolism
Receptor Activator of Nuclear Factor-kappa B
Transforming Growth Factor beta / metabolism*
p38 Mitogen-Activated Protein Kinases
|
| IF |
4.238
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224) |
