title: Secreted phospholipase A2 type II is present in Paget's disease of bone and modulates osteoclastogenesis, apoptosis and bone resorption of human osteoclasts independently of its catalytic activity in vitro.
abstract: OBJECTIVE
  To study the role of secreted phospholipase A2 (sPLA2) in the pathophysiology of human osteoclasts (OCs).
  
  
  METHODS
  Immunohistochemistry and sPLA2 inhibitors were to determine the localization of sPLA2 and its role in OCs biology.
  
  
  RESULTS
  sPLA2 is expressed by OCs from healthy fetal bone and OCs from Paget's disease but not in normal bone. Inhibition of sPLA2 greatly reduces in vitro osteoclastogenesis.
  
  
  CONCLUSIONS
  The decrease in OCs formed could be attributed to a decline in the viability of CD14(+) OC precursors as well as a reduced viability of mature OCs. Inhibition of sPLA2 strongly decreases bone resorption by OCs independently of actin cytoskeleton remodeling, probably also by reducing OCs viability.
  
  
  CONCLUSIONS
  High amounts of this enzyme are present in fetal and Pagetic bone samples. Inhibition of sPLA2in vitro decreases osteoclastogenesis and OC activity and might constitute an interesting pharmacologic target for diseases with high bone turnover.
authors.affiliation: Division of Rheumatology, Faculté de médecine et des sciences de la santé, Centre de Recherche Clinique Étienne-Le Bel, Université de Sherbrooke, 3001-12e Avenue Nord, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: Hugues
authors.initials: H
authors.lastname: Allard-Chamard
authors.affiliation: Division of Rheumatology, Faculté de médecine et des sciences de la santé, Centre de Recherche Clinique Étienne-Le Bel, Université de Sherbrooke, 3001-12e Avenue Nord, Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: Sonia
authors.initials: S
authors.lastname: Haroun
authors.affiliation: Division of Rheumatology, Faculté de médecine et des sciences de la santé, Centre de Recherche Clinique Étienne-Le Bel, Université de Sherbrooke, 3001-12e Avenue Nord, Sherbrooke, Québec, Canada J1H 5N4. Electronic address: artur.fernandes@usherbrooke.ca.
authors.forename: Artur J
authors.initials: AJ
authors.lastname: de Brum-Fernandes
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001862:Bone Resorption / Q000378:metabolism*; D002384:Catalysis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D010001:Osteitis Deformans / Q000378:metabolism* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; C059778:7,7-dimethyl-5,8-eicosadienoic acid; D054501:Group II Phospholipases A2
keywords: Bone; Osteoclasts; Paget's disease of bone; Phospholipase A2