title: Moonlighting osteoclasts as undertakers of apoptotic cells.
abstract: Rapid clearance of apoptotic cells, frequently referred to as efferocytosis, is crucial for the maintenance of tissue homeostasis and the prevention of autoimmunity. The common model of apoptotic cell clearance involves a system of released "Find me" and exposed "Eat me" signals on apoptotic cells, detected and recognized by matching receptors on macrophages or dendritic cells (DC), referred to as the phagocytic synapse. Osteoclasts share the monocyte lineage with these professional mononuclear phagocytes, thus raising the question if, in addition to bone resorption, osteoclasts can act as scavengers for apoptotic cells. Our qPCR data clearly show that osteoclasts express most of the genes required for dying cell clearance at mRNA levels similar to or even higher than those observed in M1-macrophages, M2-macrophages or DC. Our microscopical analyses reveal that osteoclasts in fact can bind and/or engulf apoptotic cells in an essentially serum-independent fashion. Together with our data on the abundance of the respective mRNAs, these results identify the vitronectin receptor (integrin α(ν)β(3))/milk fat globule-EGF factor 8 protein (MFG-E8) axis, the scavenger receptors (CD36, CD68 and class A macrophage scavenger receptor (SR-A)), the complement/complement receptor axis, the Mer/Tyro3/Protein S axis, and the phosphatidylserine (PS) receptor brain-specific angiogenesis inhibitor 1 (BAI1) as the most promising candidates to be involved in osteoclast-mediated efferocytosis.
authors.affiliation: Department of Internal Medicine-3 and Institute for Clinical Immunology, University Hospital Erlangen, Germany. ulrike.harre@uk-erlangen.de
authors.forename: Ulrike
authors.initials: U
authors.lastname: Harre
authors.forename: Hildegard
authors.initials: H
authors.lastname: Keppeler
authors.forename: Natacha
authors.initials: N
authors.lastname: Ipseiz
authors.forename: Anja
authors.initials: A
authors.lastname: Derer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Poller
authors.forename: Michael
authors.initials: M
authors.lastname: Aigner
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology; D018955:CD36 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008894:Milk Proteins / Q000378:metabolism; D010010:Osteoclasts / Q000502:physiology*; D010587:Phagocytosis; D017293:Protein S / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D051116:Receptors, Scavenger / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D042501:Angiogenic Proteins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000954:Antigens, Surface; D018955:CD36 Antigens; D039302:Integrin alphaVbeta3; D008894:Milk Proteins; D017293:Protein S; D020794:Receptor Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D051116:Receptors, Scavenger; C468226:ADGRB1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C098942:MFGE8 protein, human; C408123:phosphatidylserine receptor; C084944:TYRO3 protein, human