title: The architecture of the adhesive apparatus of cultured osteoclasts: from podosome formation to sealing zone assembly.
abstract: BACKGROUND
  Osteoclasts are bone-degrading cells, which play a central role in physiological bone remodeling. Unbalanced osteoclast activity is largely responsible for pathological conditions such as osteoporosis. Osteoclasts develop specialized adhesion structures, the so-called podosomes, which subsequently undergo dramatic reorganization into sealing zones. These ring-like adhesion structures, which delimit the resorption site, effectively seal the cell to the substrate forming a diffusion barrier. The structural integrity of the sealing zone is essential for the cell ability to degrade bone, yet its structural organization is poorly understood.
  
  
  RESULTS
  Combining high-resolution scanning electron microscopy with fluorescence microscopy performed on the same sample, we mapped the molecular architecture of the osteoclast resorptive apparatus from individual podosomes to the sealing zone, at an unprecedented resolution. Podosomes are composed of an actin-bundle core, flanked by a ring containing adhesion proteins connected to the core via dome-like radial actin fibers. The sealing zone, hallmark of bone-resorbing osteoclasts, consists of a dense array of podosomes communicating through a network of actin filaments, parallel to the substrate and anchored to the adhesive plaque domain via radial actin fibers.
  
  
  CONCLUSIONS
  The sealing zone of osteoclasts cultured on bone is made of structural units clearly related to individual podosomes. It differs from individual or clustered podosomes in the higher density and degree of inter-connectivity of its building blocks, thus forming a unique continuous functional structure connecting the cell to its extracellular milieu. Through this continuous structure, signals reporting on the substrate condition may be transmitted to the whole cell, modulating the cell response under physiological and pathological conditions.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Luxenburg
authors.forename: Dafna
authors.initials: D
authors.lastname: Geblinger
authors.forename: Eugenia
authors.initials: E
authors.lastname: Klein
authors.forename: Karen
authors.initials: K
authors.lastname: Anderson
authors.forename: Dorit
authors.initials: D
authors.lastname: Hanein
authors.forename: Benny
authors.initials: B
authors.lastname: Geiger
authors.forename: Lia
authors.initials: L
authors.lastname: Addadi
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D051419:Paxillin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D051419:Paxillin; D011993:Recombinant Fusion Proteins