Phosphate provides an extracellular signal that drives nuclear export of Runx2/Cbfa1 in bone cells.
Inorganic phosphate (Pi) supplement is generally used to accelerate mineralization of cultured bone cells but the mechanism of action is totally unknown. How the action is related with the transactivation of Runx2/Cbfa1,a master gene product of bone formation,was examined. Clonal bone cells (osteoblastic MC3T3-E1, chondrocytic ATDC5 and osteocytic MLO-Y4) on preculture in ascorbate-containing medium constantly expressed and accumulated Cbfa1 in the nuclei, and subsequent increase of Pi concentration to 3 or 10 mM was found to invariably induce nuclear export (not import) of Cbfa1 which was completed in a few hours. In addition, Pi was found to lower the expression of osteocalcin. Leptomycin B completely inhibited Pi-induced nuclear export, suggesting that CRM1/exportin 1 is involved in Pi-induced nuclear export. The result suggests that bone cells are equipped with a novel Pi sensing mechanism which is functionally linked to a nuclear export system of Cbfa1.
Fujita
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka, Japan.
Izumo
N
N
Fukuyama
R
R
Meguro
T
T
Nakamuta
H
H
Kohno
T
T
Koida
M
M
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D028884:Karyopherins; D007700:Kinetics; D051379:Mice; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010011:Osteocytes / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D000097606:Exportin 1 Protein
D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010710:Phosphates; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C038753:leptomycin B