Phosphate provides an extracellular signal that drives nuclear export of Runx2/Cbfa1 in bone cells

Inorganic phosphate (Pi) supplement is generally used to accelerate mineral ization of cultured bone cells but the mechanism of action is totally unkno wn. How the action is related with the transactivation of Runx2/Cbfa1, a ma ster gene product of bone formation, was examined. Clonal bone cells (osteo blastic MC3T3-E1, chondrocytic ATDC5 and osteocytic MLO-Y4) on preculture i n 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 c ompleted 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 m echanism which is functionally linked to a nuclear export system of Cbfa1. (C) 2001 Academic Press.