I. Nakamura et al., WORTMANNIN, A SPECIFIC INHIBITOR OF PHOSPHATIDYLINOSITOL-3 KINASE, BLOCKS OSTEOCLASTIC BONE-RESORPTION, FEBS letters, 361(1), 1995, pp. 79-84
The biological role of phosphatidylinositol (PI)-3 kinase was examined
in osteoclast-like multinucleated cells (OCLs) formed in co-cultures
of mouse osteoblastic cells and bone marrow cells. The expression of P
I-3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin
(WT), a specific inhibitor of PI-3 kinase, inhibited PI-3 kinase activ
ity in OCLs both in vitro and in vivo. WT also inhibited pit-forming a
ctivity on dentine slices and disrupted a ringed structure of F-actin-
containing dots (an actin ring) in OCLs in a dose-dependent manner. Th
e inhibitory profiles of WT for pit and actin ring formation were simi
lar to that for PI-3 kinase activity in OCLs. Electron microscopic ana
lysis revealed that OCLs treated with WT did not form ruffled borders.
Instead, numerous electron lucent vacuoles of differing sizes were fo
und throughout the cytoplasm. These results suggest that PI-3 kinase i
s important in osteoclastic bone resorption.