| RRC ID |
1452
|
| 著者 |
Niida S, Kondo T, Hiratsuka S, Hayashi S, Amizuka N, Noda T, Ikeda K, Shibuya M.
|
| タイトル |
VEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice.
|
| ジャーナル |
Proc Natl Acad Sci U S A
|
| Abstract |
VEGF receptor 1 (VEGFR-1/Flt-1) is a high-affinity tyrosine kinase (TK) receptor for VEGF and regulates angiogenesis as well as monocyte/macrophage functions. We previously showed that the osteoclast deficiency in osteopetrotic Csf1op/Csf1op (op/op) mice is gradually restored in an endogenous, VEGF-dependent manner. However, the molecular basis of the recovery is still not clear. To examine which VEGFR is important and to clarify how colony-stimulating factor 1 (CSF-1) and VEGF signals interact in osteoclastogenesis, we introduced a VEGFR-1 signaling deficiency (Flt1(TK)-/-) into op/op mice. The original Flt1(TK)-/- mice showed mild osteoclast reduction without bone marrow suppression. The double mutant (op/opFlt1(TK)-/-) mice, however, exhibited very severe osteoclast deficiency and did not have numbers of osteoclasts sufficient to form the bone marrow cavity. The narrow bone marrow cavity in the op/opFlt1(TK)-/- mice was gradually replaced with fibrous tissue, resulting in severe marrow hypoplasia and extramedullary hematopoiesis. In addition to osteoclasts, osteoblasts also decreased in number in the op/opFlt1(TK)-/- mice. These results strongly suggest that the interaction of signals by means of VEGFR-1 and the CSF-1 receptor plays a predominant role not only in osteoclastogenesis but also in the maintenance of bone marrow functions.
|
| 巻・号 |
102(39)
|
| ページ |
14016-21
|
| 公開日 |
2005-9-27
|
| DOI |
10.1073/pnas.0503544102
|
| PII |
0503544102
|
| PMID |
16172397
|
| PMC |
PMC1236539
|
| MeSH |
Animals
Bone Marrow / growth & development*
Bone Marrow / pathology
Cell Communication
Cell Differentiation / genetics
Cell Differentiation / physiology
Female
Macrophage Colony-Stimulating Factor / deficiency*
Macrophage Colony-Stimulating Factor / genetics
Male
Mice
Mice, Mutant Strains
Osteoblasts / cytology
Osteoblasts / physiology
Osteoclasts / cytology
Osteoclasts / physiology*
Primary Myelofibrosis / genetics*
Primary Myelofibrosis / pathology
Protein Structure, Tertiary
Receptor, Macrophage Colony-Stimulating Factor / metabolism
Signal Transduction
Vascular Endothelial Growth Factor Receptor-1 / genetics
Vascular Endothelial Growth Factor Receptor-1 / metabolism*
|
| IF |
9.412
|
| 引用数 |
85
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
OP9(RCB1124) |
