Wortmannin inhibits spreading and chemotaxis of rat osteoclasts in vitro

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
M F PilkingtonS J Dixon

Abstract

Wortmannin (WT) and 17beta-hydroxywortmannin (HWT), which are inhibitors of phosphatidylinositol-3(OH)-kinase (PI3K), have been shown previously to inhibit bone resorption in vitro and in vivo, possibly by interfering with formation of the osteoclast ruffled border. Since migration of osteoclasts also plays an important role in the process of bone resorption, we investigated the effects of these inhibitors on osteoclast morphology and motility. Both HWT and WT caused a sustained decrease in the planar area of osteoclasts in vitro (half maximal effect at 25 and 165 nM, respectively), with the effect of HWT on cell area more readily reversible than WT. These agents also caused accumulation of intracellular vesicles. Time-lapse video microscopy was used to record the migration of osteoclasts in response to macrophage colony-stimulating factor (M-CSF) or vehicle, flowing passively from a micropipette positioned 200-400 microm from the cell. M-CSF caused directed migration of osteoclasts, indicating chemotaxis (over 3 h osteoclasts migrated 96 +/- 14 microm in response to M-CSF vs. 11 +/- 2 microm in control experiments). Both WT (100 or 500 nM) and LY294002 (100 microM), a specific PI3K inhibitor structurally unrelated to WT, signi...Continue Reading

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Citations

Sep 24, 2002·Seminars in Cell & Developmental Biology·Gudrun Stenbeck
Jan 19, 2010·The Journal of Biological Chemistry·Brooke K McMichaelBeth S Lee
Nov 26, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Y Abu-AmerF P Ross
Jul 14, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·M F PilkingtonS J Dixon
Jan 31, 2004·Bone·Lauren H Golden, Karl L Insogna
Jan 7, 2011·The Angle Orthodontist·Patricia J BrooksSiew-Ging Gong
Sep 29, 2000·Biochemical Pharmacology·B BoyerN Edme
Sep 28, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Frédéric SaltelEdith Bonnelye
Mar 29, 2007·Journal of Cellular Biochemistry·Azza GramounMorris F Manolson
May 28, 2010·Journal of Cellular Biochemistry·Azza GramounMorris F Manolson
Jan 18, 2019·Journal of Cellular Physiology·Yexin WangShanyong Zhang
Jan 20, 2006·Cell Motility and the Cytoskeleton·Ann P WheelerAnne J Ridley
Apr 11, 2007·The Journal of Biological Chemistry·Roberta FaccioF Patrick Ross
Jul 9, 2020·Frontiers in Cell and Developmental Biology·Dávid S Győri, Attila Mócsai
Apr 30, 2020·Journal of Cellular and Molecular Medicine·Jin CuiJiacan Su
Apr 15, 2000·The Journal of Biological Chemistry·M A ChellaiahK A Hruska
Nov 18, 2005·Journal of Cell Science·Beatrice B YaroslavskiyHarry C Blair

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