We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70.
- Authors
Garbe, Annette I; Roscher, Anne; Schüler, Christiane; Lutter, Anne-Helen; Glösmann, Martin; Bernhardt, Ricardo; Chopin, Michael; Hempel, Ute; Hofbauer, Lorenz C; Rammelt, Stefan; Egerbacher, Monika; Erben, Reinhold G; Jessberger, Rolf
- 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.
- Subjects
BONE density; BONE physiology; OSTEOCLASTS; F-actin; RESORPTION (Physiology); MACROPHAGE colony-stimulating factor; BIOMARKERS
- Publication
Journal of Bone & Mineral Research, 2012, Vol 27, Issue 10, p2085
- ISSN
0884-0431
- Publication type
Article
- DOI
10.1002/jbmr.1670