ECTS2013 Poster Presentations Cell biology: osteoclasts and bone resorption (24 abstracts)
The F-actin modulator SWAP-70 is required for proper podosome dynamics in osteoclasts
Anne Roscher 1 , Martin Glösmann 2 , Reinhold G Erben 2 , Anne-Helen Lutter 1 , Michael Chopin 1 , Lorenz C Hofbauer 3 , Rolf Jessberger 1 & Annette Garbe 1
1Institute of Physiological Chemistry, Dresden University of Technology, Dresden, Germany; 2Department of Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria; 3Division of Endocrinology and Bone Diseases, Dresden University Medical Center, Dresden, Germany.
Bone remodeling is a crucial process to maintain a healthy bone structure in order to avoid diseases like osteoporosis or osteopetrosis. Osteoclasts contribute to this process by resorbing old and brittle bone allowing osteoblasts to renew the bone substance. During resorption osteoclasts rearrange their actin cytoskeleton by forming an F-actin ring generating a resorptive cavity on the bone surface. Recently, we reported that the F-actin binding protein SWAP-70 regulates osteoclast function by modulating the actin cytoskeleton. Swap-70−/− osteoclasts fail to form an F-actin ring resulting in diminished resorptive function, while cytokine induced osteoclast differentiation markers remain unchanged. Swap-70−/− mice develop osteopetrosis characterized by increased bone mineral density and impaired osteoclast function. SWAP-70-proficient bone marrow transplantation into Swap-70−/− mice restores osteoclast resorption capacity in vivo suggesting that the osteoclast defect is intrinsic. Ectopic expression of SWAP-70 in Swap-70−/− osteoclasts in vitrorestores F-actin ring formation and osteoclast function. By expression of SWAP-70 variants we show that a functional pleckstrin homology domain as well as the acidic part of the coiled-coil region of SWAP-70 are indispensable for osteoclast function.
We now have evidence that Swap-70−/− osteoclasts fail to cluster podosomes during osteoclastogenesis and are impaired in organizing podosome-based F-actin rings and an F-actin belt. These data identify SWAP-70 as a crucial player of podosome dynamics in osteoclasts.
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Bone Abstracts
ISSN 2052-1219 (online)
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