Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70 |
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Authors: | Annette I Garbe Christiane Schüler Anne‐Helen Lutter Martin Glösmann Ricardo Bernhardt Michael Chopin Ute Hempel Lorenz C Hofbauer Stefan Rammelt Monika Egerbacher Reinhold G Erben Rolf Jessberger |
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Affiliation: | Institute of Physiological Chemistry, Dresden University of Technology, Dresden, Germany. annette.garbe@tu-dresden.de. |
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Abstract: | Bone remodeling involves tightly regulated bone‐resorbing osteoclasts and bone‐forming osteoblasts. Determining osteoclast function is central to understanding bone diseases such as osteoporosis and osteopetrosis. Here, we report a novel function of the F‐actin binding and regulatory protein SWAP‐70 in osteoclast biology. F‐actin ring formation, cell morphology, and bone resorption are impaired in Swap‐70?/? osteoclasts, whereas the expression of osteoclast differentiation markers induced in vitro by macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL) remains unaffected. Swap‐70?/? mice develop osteopetrosis with increased bone mass, abnormally dense bone, and impaired osteoclast function. Ectopic expression of SWAP‐70 in Swap‐70?/? osteoclasts in vitro rescues their deficiencies in bone resorption and F‐actin ring formation. Rescue requires a functional pleckstrin homology (PH) domain, known to support membrane localization of SWAP‐70, and the F‐actin binding domain. Transplantation of SWAP‐70–proficient bone marrow into Swap‐70?/? mice restores osteoclast resorption capacity in vivo. The identification of the role of SWAP‐70 in promoting osteoclast function through modulating membrane‐proximal F‐actin rearrangements reveals a new pathway to control osteoclasts and bone homeostasis. © 2012 American Society for Bone and Mineral Research. |
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Keywords: | BONE OSTEOCLASTS F‐ACTIN RESORPTION SWAP‐70 |
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