title: The cell biology of osteoclast function.
abstract: Osteoclasts are multinucleated cells responsible for bone resorption. They have developed an efficient machinery for dissolving crystalline hydroxyapatite and degrading organic bone matrix rich in collagen fibers. When initiating bone resorption, osteoclasts become polarized, and three distinct membrane domains appear: a ruffled border, a sealing zone and a functional secretory domain. Simultaneously, the cytoskeleton undergoes extensive re-organisation. During this process, the actin cytoskeleton forms an attachment ring at the sealing zone, the membrane domain that anchors the resorbing cell to bone matrix. The ruffled border appears inside the sealing zone, and has several characteristics of late endosomal membrane. Extensive vesicle transport to the ruffled border delivers hydrochloric acid and proteases to an area between the ruffled border and the bone surface called the resorption lacuna. In this extracellular compartment, crystalline hydroxyapatite is dissolved by acid, and a mixture of proteases degrades the organic matrix. The degradation products of collagen and other matrix components are endocytosed, transported through the cell and exocytosed through a functional secretory domain. This transcytotic route allows osteoclasts to remove large amounts of matrix-degradation products without losing their tight attachment to underlying bone. It also facilitates further processing of the degradation products intracellularly during the passage through the cell.
authors.affiliation: Skeletal Research Program, Department of Anatomy, Institute of Biomedicine, University of Turku, Finland. kalervo.vaananen@utu.fi
authors.forename: H K
authors.initials: HK
authors.lastname: Väänänen
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Mulari
authors.forename: J M
authors.initials: JM
authors.lastname: Halleen
mesh_terms: D000818:Animals; D001692:Biological Transport; D001857:Bone Matrix / Q000378:metabolism; D001862:Bone Resorption / Q000473:pathology*; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000648:ultrastructure; D017886:Durapatite / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D006851:Hydrochloric Acid / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015388:Organelles / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology* / Q000502:physiology; D017494:Proton Pumps / Q000378:metabolism; D017382:Reactive Oxygen Species
chemical_list: D017494:Proton Pumps; D017382:Reactive Oxygen Species; D003094:Collagen; D017886:Durapatite; D010450:Endopeptidases; D006851:Hydrochloric Acid