z-logo
Premium
Regulation of bone mass and osteoclast function depend on the F‐actin modulator SWAP‐70
Author(s) -
Garbe Annette I,
Roscher Anne,
Schüler Christiane,
Lutter AnneHelen,
Glösmann Martin,
Bernhardt Ricardo,
Chopin Michael,
Hempel Ute,
Hofbauer Lorenz C,
Rammelt Stefan,
Egerbacher Monika,
Erben Reinhold G,
Jessberger Rolf
Publication year - 2012
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.1670
Subject(s) - osteoclast , swap (finance) , microbiology and biotechnology , function (biology) , chemistry , medicine , biology , business , receptor , finance
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.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here