Discrete types of osteoclast precursors can be generated from embryonic stem cells.
Osteoclast precursors (OCPs) share some characteristics with the monocyte/macrophage lineages, but the early events of OCP development are not yet clear. To investigate osteoclastogenesis from the earliest stage, we used step-wise cultures of embryonic stem (ES) cells to induce mature osteoclasts and assessed the effect of vascular endothelial growth factor receptor (VEGFR)-1/Fc chimeric protein on osteoclast development. Addition of VEGFR-1/Fc for the first 5 days of culture (phase I) severely inhibited the development of OCPs. Although OCPs were detected after culturing for a further 5 days (phase II), the reduction of OCPs in phase I was maintained in phase II. The generation of OCPs in phase I was resistant to signal blocking mediated by Kit receptors, but that in phase II was partially inhibited by either an anti-Kit antagonistic antibody or VEGFR-1/Fc and was severely inhibited by the combination of both reagents. Moreover, the OCPs in phase I gave rise to larger numbers of osteoclasts but required a longer period for maturation than the OCPs in phase II. We thus showed that OCPs expanded in phase II, but the majority of OCPs arose from ES cells in a manner dependent on VEGFR-1 binding factor(s) in phase I.
Division of Immunology, Department of Molecular and Cellular Biology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
Hiromi
H
Okuyama
Motokazu
M
Tsuneto
Toshiyuki
T
Yamane
Hidetoshi
H
Yamazaki
Shin-Ichi
S
Hayashi
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000166:cytology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors
D040281:Vascular Endothelial Growth Factor Receptor-1