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

J Bone Miner Res. 2012 Oct;27(10):2085-96. doi: 10.1002/jbmr.1670.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Minor Histocompatibility Antigens
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / metabolism*
  • Organ Size
  • Osteoblasts / pathology
  • Osteoclasts / metabolism*
  • Osteoclasts / pathology*
  • Osteopetrosis / complications
  • Osteopetrosis / pathology


  • Actins
  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • Swap70 protein, mouse