Premium
Wortmannin, a specific inhibitor of phosphatidylinositol‐3 kinase, blocks osteoclastic bone resorption
Author(s) -
Nakamura Ichiro,
Takahashi Naoyuki,
Sasaki Takahisa,
Tanaka Sakae,
Udagawa Nobuyuki,
Murakami Hiroshi,
Kimura Koutaro,
Kabuyama Yukihito,
Kurokawa Takahide,
Suda Tatsuo,
Fukui Yasuhisa
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00153-z
Subject(s) - wortmannin , phosphatidylinositol , bone resorption , osteoclast , microbiology and biotechnology , kinase , multinucleate , pi , cytoplasm , actin , biology , chemistry , in vitro , biochemistry , endocrinology
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 PI‐3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin (WT), a specific inhibitor of PI‐3 kinase, inhibited PI‐3 kinase activity in OCLs both in vitro and in vivo. WT also inhibited pit‐forming activity on dentine slices and disrupted a ringed structure of F‐actin‐containing dots (an actin ring) in OCLs in a dose‐dependent manner. The inhibitory profiles of WT for pit and actin ring formation were similar to that for PI‐3 kinase activity in OCLs. Electron microscopic analysis revealed that OCLs treated with WT did not form ruffled borders. Instead, numerous electron lucent vacuoles of differing sizes were found throughout the cytoplasm. These results suggest that PI‐3 kinase is important in osteoclastic bone resorption.