Osteogenic differentiation of the mesenchymal progenitor cells, Kusa is suppressed by Notch signaling.
Notch receptor plays a crucial role in proliferation and differentiation of many cell types. To elucidate the function of Notch signaling in osteogenesis, we transfected the constitutively active Notch1 (Notch intracellular domain, NICD) into two different osteoblastic mesenchymal cell lines, KusaA and KusaO, and examined the changes of their osteogenic potentials. In NICD stable transformants (KusaA(NICD) and KusaO(NICD)), osteogenic properties including alkaline phosphatase activity, expression of osteocalcin and type I collagen, and in vitro calcification were suppressed. Transient transfection of NICD attenuated the promoter activities of Cbfa1 and Ose2 element. KusaA was capable of forming trabecular bone-like tissues when injected into mouse abdomen, but this in vivo bone forming activity was significantly suppressed in KusaA(NICD). Osteoclasts were induced in the KusaA-derived bone-like tissues, but lacked in the KusaA(NICD)-derived tissues. These results suggest that Notch signaling suppresses the osteoblastic differentiation of mesenchymal progenitor cells.
Shindo
Kentaro
K
Pulp Biology and Endodontics, Graduate School of Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. k.shindo.endo@tmd.ac.jp
Kawashima
Nobuyuki
N
Sakamoto
Kei
K
Yamaguchi
Akira
A
Umezawa
Akihiro
A
Takagi
Minoru
M
Katsube
Ken-ichi
K
Suda
Hideaki
H
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers / Q000737:chemistry; D005819:Genetic Markers; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009024:Morphogenesis; D009363:Neoplasm Proteins; D010012:Osteogenesis; D011401:Promoter Regions, Genetic / Q000235:genetics; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D017931:DNA Primers; D005819:Genetic Markers; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D008156:Luciferases; D002118:Calcium