To clarify the role of Fms-like tyrosine kinase-1 (Flt-1) signaling in bone dynamics, we examined C57BL/6J mice, aged 6, 9 and 16 weeks, with disruption of the flt1 tyrosine kinase domain gene (flt1(TK-/-)) and compared with age-matched wild-type (flt1(TK+/+)) mice. Dynamic histomorphometric analysis confirmed a significant decrease in the values of mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) in the trabecular bone of the proximal tibiae of flt1(TK-/-) mice compared with those in flt1(TK+/+) mice. The value of trabecular bone volume (BV/TV) was also significantly reduced in flt1(TK-/-) mice compared with that in flt1(TK+/+) mice. The values of osteoclast surface (Oc.S/BS) and osteoclast number (Oc.N/BS) in flt1(TK-/-) mice were somewhat lower than those in flt1(TK+/+) mice. The values of bending load of the femur significantly decreased in flt1(TK-/-) mice. In addition, serum osteocalcin significantly decreased in flt1(TK-/-) mice compared with those in flt1(TK+/+) mice. Furthermore, there was a significant decreased mineralization of bone marrow stromal cultures from flt1(TK-/-) mice. These findings demonstrate that flt1(TK-/-) mice show lower trabecular bone volume than flt1(TK+/+) mice, providing powerful evidence that vascular endothelial growth factor signal pathway through the Flt-1 tyrosine kinase domain could be implicated in osteoblast development.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bone.2007.02.007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification and characterization of VEGF-A-responsive neutrophils expressing CD49d, VEGFR1, and CXCR4 in mice and humans.
Blood
October 2015
Department of Medical Cell Biology and.
Vascular endothelial growth factor A (VEGF-A) is upregulated during hypoxia and is the major regulator of angiogenesis. VEGF-A expression has also been found to recruit myeloid cells to ischemic tissues where they contribute to angiogenesis. This study investigates the mechanisms underlying neutrophil recruitment to VEGF-A as well as the characteristics of these neutrophils.
View Article and Find Full Text PDFVEGFR-1 regulates adult olfactory bulb neurogenesis and migration of neural progenitors in the rostral migratory stream in vivo.
J Neurosci
July 2009
Goethe University Medical School, Institute of Neurology (Edinger Institute), Neuroscience Center, 60528 Frankfurt am Main, Germany.
The generation of new neurons in the olfactory bulb (OB) persists into adulthood and is a multistep process that includes proliferation, fate choice, migration, survival, and differentiation. Neural precursor cells destined to form olfactory interneurons arise in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) to the OB. Recently, some factors classically known from their effects on the vascular system have been found to influence different steps of adult neurogenesis.
View Article and Find Full Text PDFFlt-1 tyrosine kinase-deficient homozygous mice result in decreased trabecular bone volume with reduced osteogenic potential.
Bone
June 2007
Department of Orthopaedic Surgery, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
To clarify the role of Fms-like tyrosine kinase-1 (Flt-1) signaling in bone dynamics, we examined C57BL/6J mice, aged 6, 9 and 16 weeks, with disruption of the flt1 tyrosine kinase domain gene (flt1(TK-/-)) and compared with age-matched wild-type (flt1(TK+/+)) mice. Dynamic histomorphometric analysis confirmed a significant decrease in the values of mineralizing surface (MS/BS), mineral apposition rate (MAR), and bone formation rate (BFR/BS) in the trabecular bone of the proximal tibiae of flt1(TK-/-) mice compared with those in flt1(TK+/+) mice. The value of trabecular bone volume (BV/TV) was also significantly reduced in flt1(TK-/-) mice compared with that in flt1(TK+/+) mice.
View Article and Find Full Text PDFVEGF receptor 1 signaling is essential for osteoclast development and bone marrow formation in colony-stimulating factor 1-deficient mice.
Proc Natl Acad Sci U S A
September 2005
Department of Bone and Joint Disease, Research Institute, National Center for Geriatrics and Gerontology, Aichi 474-8522, Japan.
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.
View Article and Find Full Text PDFFlt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice.
Proc Natl Acad Sci U S A
August 1998
Department of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Receptor tyrosine kinases Flt-1 and Flk-1/KDR, and their ligand, the vascular endothelial growth factor (VEGF), were shown to be essential for angiogenesis in the mouse embryo by gene targeting. Flk-1/KDR null mutant mice exhibited impaired endothelial and hematopoietic cell development. On the other hand, Flt-1 null mutation resulted in early embryonic death at embryonic day 8.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!