1,25-dihydroxyvitamin D-3 induces the expression of vascular endothelial growth factor in osteoblastic cells.

被引:63
作者
Schlaeppi, JM [1 ]
Gutzwiller, S [1 ]
Finkenzeller, G [1 ]
Fournier, B [1 ]
机构
[1] TUMOR BIOL CTR,INST MOL MED,D-79106 FREIBURG,GERMANY
关键词
D O I
10.3109/07435809709031855
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Angiogenesis is a fundamental process in skeletal development and repair, and previous studies indicate that vascular endothelial growth factor (VEGF), an endothelial cell-specific angiogenic factor, may be involved in bone formation and repair. Therefore, we studied the hormonal regulation of VEGF expression in SaOS-2 osteoblast-like cells, both at the protein level, and at the transcriptional level by transient transfection experiments. 1,25-Dihydroxyvitamin D-3 [1,25-(OH)(2)D-3], increased VEGF expression by approximately 3-fold, and the increase was dose dependent, with maximum stimulation between 1.0 and 10 nM of 1,25-(OH)(2)D-3. Up-regulation of VEGF protein was detected already after 6 h of treatment. VEGF up-regulation was also observed in ROS-17/2.8 and OHS-4 osteoblast-like cells but not in MCF-7 and MDA-MB231 breast carcinoma cells. Dexamethasone (Dex) decreased VEGF expression to 40% of the control, but when added together with 1,25-(OH)(2)D-3, had no effects on the up-regulation of VEGF by 1,25-(OH)(2)D-3. PTH1-34 stimulated weakly VEGF expression, but combined with 1,25-(OH)(2)D-3, resulted in a close to 5-fold stimulation. A 4-day pretreatment of the cells with Dex increased the vitamin D-3 receptor expression and resulted in a stronger stimulation of VEGF by 1,25-(OH)(2)D-3, alone or in combination with PTH1-34. The results show that the VEGF promoter is a target of 1,25-(OH)(2)D-3 regulation in osteoblasts, despite the lack of classical vitamin D-3 responsive elements. The up-regulation of VEGF in osteoblast-like cells by calciotropic hormones provides additional evidence of the involvement of VEGF in bone metabolism.
引用
收藏
页码:213 / 229
页数:17
相关论文
共 38 条
[1]  
BRIGHTON CT, 1978, CLIN ORTHOP RELAT R, V136, P22
[2]   CHANGES IN TRABECULAR BONE, HEMATOPOIESIS AND BONE-MARROW VESSELS IN APLASTIC-ANEMIA, PRIMARY OSTEOPOROSIS, AND OLD-AGE - A COMPARATIVE HISTOMORPHOMETRIC STUDY [J].
BURKHARDT, R ;
KETTNER, G ;
BOHM, W ;
SCHMIDMEIER, M ;
SCHLAG, R ;
FRISCH, B ;
MALLMANN, B ;
EISENMENGER, W ;
GILG, T .
BONE, 1987, 8 (03) :157-164
[3]   MECHANISMS OF NUCLEAR SIGNALING BY VITAMIN-D-3 - INTERPLAY WITH RETINOID AND THYROID-HORMONE SIGNALING [J].
CARLBERG, C .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1995, 231 (03) :517-527
[4]  
CHEN TL, 1986, ENDOCRINOLOGY, V118, P1119, DOI 10.1210/endo-118-3-1119
[5]   VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR EXPRESSION IN THE RAT UTERUS - RAPID STIMULATION BY ESTROGEN CORRELATES WITH ESTROGEN-INDUCED INCREASES IN UTERINE CAPILLARY-PERMEABILITY AND GROWTH [J].
CULLINANBOVE, K ;
KOOS, RD .
ENDOCRINOLOGY, 1993, 133 (02) :829-837
[6]   THE FMS-LIKE TYROSINE KINASE, A RECEPTOR FOR VASCULAR ENDOTHELIAL GROWTH-FACTOR [J].
DEVRIES, C ;
ESCOBEDO, JA ;
UENO, H ;
HOUCK, K ;
FERRARA, N ;
WILLIAMS, LT .
SCIENCE, 1992, 255 (5047) :989-991
[7]  
DVORAK HF, 1995, AM J PATHOL, V146, P1029
[8]   THE ROLE OF VASCULAR ENDOTHELIAL GROWTH-FACTOR IN PATHOLOGICAL ANGIOGENESIS [J].
FERRARA, N .
BREAST CANCER RESEARCH AND TREATMENT, 1995, 36 (02) :127-137
[9]   MOLECULAR AND BIOLOGICAL PROPERTIES OF THE VASCULAR ENDOTHELIAL GROWTH-FACTOR FAMILY OF PROTEINS [J].
FERRARA, N ;
HOUCK, K ;
JAKEMAN, L ;
LEUNG, DW .
ENDOCRINE REVIEWS, 1992, 13 (01) :18-32
[10]   SYNTHESIS AND ASSEMBLY OF FUNCTIONALLY ACTIVE HUMAN VASCULAR ENDOTHELIAL GROWTH-FACTOR HOMODIMERS IN INSECT CELLS [J].
FIEBICH, BL ;
JAGER, B ;
SCHOLLMANN, C ;
WEINDEL, K ;
WILTING, J ;
KOCHS, G ;
MARME, D ;
HUG, H ;
WEICH, HA .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 211 (1-2) :19-26