ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis and inhibits bone resorption after bone marrow ablation.
ED-71, a novel analog of 1alpha,25-(OH)2 D3, increases bone mass to a greater extent than alfacalcidol, an 1alpha,25-(OH)2 D3 prodrug. In this study, we used a murine bone marrow ablation model to compare the effect of ED-71 on bone formation and resorption in vivo with that of 1alpha,25-(OH)2 D3. We discovered that bone matrix remodeling occurring within the first week after bone marrow ablation was enhanced by a single injection of ED-71, but not by 1alpha,25-(OH)2 D3. This enhancement was associated with an increase in bone surface. Trabecular bone resorption occurring from 1 to 2 weeks after the procedure was suppressed by a single injection of ED-71, but not 1alpha,25-(OH)2 D3, with treated mice exhibiting a reduction in osteoclast numbers, despite increases in osteoblast surface. As seen with the single injection, daily administration of ED-71 also enhanced bone modeling. Bone marrow osteoblast differentiation was also augmented by ED-71 pretreatment. Furthermore, ED-71 treatment immediately after bone marrow ablation enhanced angiogenesis within the bone marrow cavity via enhancement of VEGF(120) expression. In this paper, we clearly demonstrate that ED-71 is an orally administered small molecular weight compound with an anabolic effect on bone metabolism.
Okuda
N
N
Section of Orthopeadic Surgery, Department of Molecular Regulation of Supportive Tissue, Division of Bio Matrix, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Takeda
S
S
Shinomiya
K
K
Muneta
T
T
Itoh
S
S
Noda
M
M
Asou
Y
Y
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D001842:Bone and Bones / Q000098:blood supply*; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives; D014815:Vitamins / Q000008:administration & dosage / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D014815:Vitamins; C467480:vascular endothelial growth factor A, mouse; D014807:Vitamin D; D002117:Calcitriol; C547512:eldecalcitol