title: Targeting Fas in osteoresorptive disorders.
abstract: BACKGROUND
  Fas receptor is a mediator of the external apoptotic pathway in many cells and tissues. It is proposed that Fas receptor mediates osteoresorptive effects of estrogen deficiency and local/systemic inflammation.
  
  
  METHODS
  This review covers the past two decades of research on the expression and function of the Fas-Fas ligand system on bone cells, involvement in the pathogenesis of osteoresorption and potential therapeutic modulation.
  
  
  RESULTS
  We review the structure, biological function and intracellular signaling pathways of the Fas-Fas ligand system emphasizing the role of the non-apoptotic signaling pathways in bone cells, particularly osteoblast differentiation. We also present data on the in vitro expression and function of the Fas-Fas ligand system on osteoblast/osteoclast lineage cells, animal and human studies confirming its involvement in osteoresorptive disorders and potential therapeutic approaches to modulate its function.
  
  
  CONCLUSIONS
  Tissue specific therapeutic approaches need to be established to modify the Fas-Fas ligand system in osteoresorptive disorders as systemic targeting has many side effects. The most promising approach would be to target Fas signaling molecules coupled with osteoblast/osteoclast differentiation pathways, but a precise definition of these targets is still needed.
authors.affiliation: University of Zagreb School of Medicine, Department of Anatomy, Zagreb, HR-10000, Croatia. natasa@mef.hr
authors.forename: Natasa
authors.initials: N
authors.lastname: Kovacic
authors.forename: Danka
authors.initials: D
authors.lastname: Grcevic
authors.forename: Vedran
authors.initials: V
authors.lastname: Katavic
authors.forename: Ivan Kresimir
authors.initials: IK
authors.lastname: Lukic
authors.forename: Ana
authors.initials: A
authors.lastname: Marusic
mesh_terms: D000818:Animals; D017209:Apoptosis; D001862:Bone Resorption / Q000235:genetics / Q000503:physiopathology*; D001842:Bone and Bones / Q000502:physiology / Q000503:physiopathology; D002454:Cell Differentiation; D019070:Cell Lineage; D053222:Fas Ligand Protein / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D015870:Gene Expression; D006801:Humans; D058990:Molecular Targeted Therapy; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D015398:Signal Transduction / Q000187:drug effects; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D053222:Fas Ligand Protein; D019014:fas Receptor