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Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2012

AutorInnen: Garbe, AI; Roscher, A; Schüler, C; Lutter, AH; Glösmann, M; Bernhardt, R; Chopin, M; Hempel, U; Hofbauer, LC; Rammelt, S; Egerbacher, M; Erben, RG; Jessberger, R

Titel: Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70.

Quelle: J Bone Miner Res. 2012; 27(10):2085-2096



Autor/innen der Vetmeduni Vienna:

Egerbacher Monika
Erben Reinhold
Glösmann Martin
Schüler Christiane

Beteiligte Vetmed-Organisationseinheiten
Institut für Physiologie, Pathophysiologie und Biophysik, Abteilung für Physiologie, Pathophysiologie und experimentelle Endokrinologie
Institut für Morphologie
VetCore


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.

Keywords Pubmed: Actins/metabolism*
Animals
Bone Resorption/complications
Bone Resorption/pathology
Bone and Bones/pathology*
Cell Line
Cell Movement
DNA-Binding Proteins/deficiency
DNA-Binding Proteins/metabolism*
Guanine Nucleotide Exchange Factors/deficiency
Guanine Nucleotide Exchange Factors/metabolism*
Humans
Mice
Nuclear Proteins/deficiency
Nuclear Proteins/metabolism*
Organ Size
Osteoblasts/pathology
Osteoclasts/metabolism*
Osteoclasts/pathology*
Osteopetrosis/complications
Osteopetrosis/pathology


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